1. ENDOCRINE AND METABOLIC DISORDERS
Suggestions for Lecturer
-1-hour lecture
-Use GRS slides alone or to supplement your own teaching materials.
-Refer to GRS for further content, including strength of evidence (SOE) levels.
-Note that diabetes mellitus and osteoporosis are addressed in separate GRS chapters and slide sets.
--See GRS8 questions 35, 43, 105, 263, 282, and 326 for case vignettes on endocrine and metabolic disorders.

2. How hormone levels change with aging
OBJECTIVES
Know and understand:
How hormone levels change with aging
Signs and symptoms that are suggestive of endocrine and metabolic disorders
Laboratory evaluation of older adults for endocrine and metabolic disorders
Treatment options and indications for hormone replacement
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3. TOPICS COVERED Thyroid Disorders
Disorders of Parathyroid and Calcium Metabolism
Hormonal Regulation of Water and Electrolyte Balance
Disorders of the Adrenal Cortex
Testosterone
Estrogen
Growth Hormone
Melatonin
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4. HOMEOSTATIC REGULATION
Impaired in many endocrine systems with aging
Loss of function in one aspect of endocrine function may result in compensatory change in endocrine regulation and be associated with alterations in hormone catabolism
In some instances, compensatory changes in regulation and alterations in hormone catabolism do not fully offset age-related impairment in endocrine function
Impaired homeostatic regulation, a hallmark of aging, occurs in many endocrine systems but may become manifest only during stress. For example, fasting blood glucose levels change little with normal aging, increasing 1 to 2 mg/dL per decade of life. In contrast, glucose levels after a glucose challenge (eg, postprandially) increase much more in healthy older people than in young adults. In some cases, a loss of function in one aspect of endocrine function may result in a compensatory change in endocrine regulation and be associated with alterations in catabolism that can maintain homeostasis. For example, the reduction in testicular testosterone production that occurs in many older men may be partially offset by an increase in pituitary luteinizing hormone secretion and a decrease in testosterone metabolism.
In other instances, compensatory changes or alterations in hormone catabolism do not fully offset age-related impairment in endocrine functions, as illustrated by the age-related decline in basal serum aldosterone levels. In this case, a decline in aldosterone clearance fails to offset the decrease in aldosterone secretion.
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5. PROBLEMS IN DIAGNOSING ENDOCRINE DISORDERS
Often present with nonspecific, muted, or atypical symptoms and signs in older adults
Complete absence of complaints is common
Lab evaluation may be complicated by coexisting illnesses and medications
For most lab tests, normal ranges for healthy older people are not available
Some endocrine disorders are seen almost exclusively in older adults and have a well-defined presentation, such as apathetic thyrotoxicosis or hyperosmolar nonketotic state in patients with diabetes mellitus. However, more commonly, endocrine disorders present with subtle, nonspecific symptoms, such as cognitive impairment, or an absence of any complaints. Indeed, the diagnosis of endocrinopathies such as hyperparathyroidism, diabetes mellitus, hypothyroidism, and hyperthyroidism in older adults is commonly established as a result of abnormalities found on routine laboratory screening.
Laboratory evaluation of older adults for endocrine disorders may be complicated by coexisting medical illnesses and medications. For example, the presence of serious acute nonthyroidal illness may lead to the mistaken impression of a thyroid disorder because of the reduction in free thyroxine levels and sometimes increased or decreased thyrotropin levels in sick but euthyroid older patients. Furthermore, ranges of normal laboratory values for endocrine testing are commonly established in younger adults, and even age-adjusted norms for laboratory tests may be confounded by the inclusion of older adults who are ill. Therefore, normal ranges for healthy older people are not available for most laboratory tests.
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6. INTRODUCTION TO THYROID DISORDERS
With normal aging:
Thyroxine (T4) levels remain unchanged
Triiodothyronine (T3) levels are unchanged until extreme old age, when they decrease slightly
Distribution of TSH levels shifts upward  higher prevalence of biochemical hypothyroidism in older adults
TSH testing recommended:
For all older adults with a recent decline in clinical, cognitive, or functional status
For patients admitted to a nursing home
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7. HYPOTHYROIDISM
Symptoms often atypical—laboratory screening necessary to detect most cases
Mild hypothyroidism + severe nonthyroidal illness can rapidly  severe hypothyroidism, myxedema coma
Subclinical hypothyroidism (elevated TSH, normal free T4 level):
Occurs in up to 15% of people ≥65; more common in women
Risk of coronary heart disease and mortality increased in people <65 but not in those >65
Overt hypothyroidism occurs in 0.5% to 5% of older adults, depending on the population studied. Subclinical hypothyroidism has been reported in up to 15% of people ≥65 yr old, and is more common in women. As in younger people, most cases of hypothyroidism in older people are due to chronic autoimmune thyroiditis.
Symptoms of hypothyroidism are often atypical in older adults. Some clinical features of hypothyroidism (eg, dry skin, decreased skin turgor, slowed mentation, weakness, constipation, anemia, hyponatremia, arthritis, paresthesias, gait disturbances, elevated myocardial band of creatine phosphokinase) may misleadingly suggest other diseases. Furthermore, these symptoms usually have an insidious onset and a slow rate of progression. As a result, the diagnosis of hypothyroidism is recognized on clinical examination in only 10% to 20% of cases in older adults, and laboratory screening is necessary to detect most cases.
Older patients with mild hypothyroidism who develop serious nonthyroidal illness may rapidly become severely hypothyroid, and older adults are more susceptible to myxedema coma in this setting. Demented older people with hypothyroidism rarely recover normal cognitive function with thyroid replacement, but cognition, functional status, and mood may improve with treatment of the hypothyroidism.
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8. POTENTIAL FOR CONFUSION IN DIAGNOSING HYPOTHYROIDISM
Low T4 syndrome
Seen in euthyroid patients with severe nonthyroidal illnesses
TSH normal, free T4 index decreased, free T4 level usually normal, reverse T3 elevated
Thyroid hormone replacement not beneficial
Secondary hypothyroidism
TSH normal or low, free T4 level low
Decreased reverse T3
Hypopituitarism
Rarely, older people with primary hypothyroidism may present with inappropriately normal TSH levels resulting from suppression of TSH by fasting, acute illnesses, and medications such as dopamine, phenytoin, or glucocorticoids.
By itself, an increased TSH level is usually due to primary hypothyroidism, but TSH may be transiently increased during recovery from acute illnesses. Therefore, the diagnosis of hypothyroidism should be confirmed by the combination of increased TSH and decreased free T4 or free T4 index, or a persistently increased TSH, or both.
To minimize confusion between thyroid disease and the nonthyroidal illness syndrome, thyroid function testing in seriously ill patients should be performed only if thyroid dysfunction is strongly suspected.
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9. MANAGEMENT OF SUBCLINICAL HYPOTHYROIDISM
Consider T4 replacement in older adults with:
Progressively increasing TSH levels
TSH persistently >10 mIU/L
Presence of high titer of antithyroid peroxidase antibodies consistent with Hashimoto disease
Associated with eventual overt hypothyroidism
In older adults, a mildly low activity of thyroid hormone may be associated with improved survival. Randomized trials of T4 supplementation in older adults with subclinical hypothyroidism have not shown a consistent improvement in symptoms, although people with TSH levels >10 mIU/L may derive symptomatic benefit.
Accordingly, T4 supplementation in older adults with mildly increased TSH levels may be of limited clinical benefit or even harmful. However, adults with TSH ≥10 mIU/L are at increased risk of coronary heart disease events and mortality regardless of age. It is unknown whether these risks can be mitigated with T4 replacement.
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10. T4 REPLACEMENT
Usually started at low dosage (eg, 25 mcg/day) and increased every 4–6 weeks until TSH normal
In patients with unstable cardiac disease, begin at even lower dosage (eg, 12.5 mcg/day)
In patients with severe hypothyroidism at presentation:
Exclude concomitant adrenal insufficiency
Give stress doses of glucocorticoids
Start at 50 to 100 mcg/day, or up to 400 mcg IV for patients with myxedema stupor or coma, even with a history of cardiac disease
Thyroid replacement should not be withheld for fear of exacerbating cardiac disease; instead, the goal is to reduce or eliminate symptoms of hypothyroidism without causing intolerable exacerbation of cardiac symptoms, such as angina.
Thyroid hormone requirements decrease with aging because of a reduction in clearance rate, and T4 replacement doses are as much as a third lower in older than in younger adults. The average T4 replacement dosage in older adults is approximately 110 mcg/day. Overreplacement of thyroid hormone should be avoided, because osteopenia related to increased bone turnover and exacerbation of heart disease may occur. With correction of the hypothyroid state, the clearance rate of medications such as anticonvulsants, digoxin, and opiate analgesic agents may be affected, necessitating dosage adjustments.
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11. HYPERTHYROIDISM In older adults in US, usually due to Graves disease
Triples the risk of developing AF within 10 years, and present in 13%–30% of older people with AF
Causes secondary osteoporosis and should be suspected in patients with low bone mineral density
Apathetic thyrotoxicosis
Characterized by depression, inactivity, lethargy, or withdrawn behavior
Often associated with weight loss, muscle weakness, or cardiac symptoms
AF = atrial fibrillation
Hyperthyroidism develops in 0.5% to 2.3% of older people, and 15% to 25% of all cases of thyrotoxicosis occur in adults aged 60 and over. In the United States, most cases in older adults are due to Graves disease, but toxic multinodular goiter and autonomously functioning adenomas are more common in older than in young adults, especially in populations with low iodine intake.
Hyperthyroidism often presents with vague, atypical, or nonspecific symptoms in frail older patients. Many findings that are common in younger adults (eg, tremor, heat intolerance, tachycardia, ophthalmopathy, increased perspiration, goiter, brisk reflexes) are less common or absent in older people, whereas other manifestations, such as AF, heart failure, constipation, anorexia, muscle atrophy, and weakness, are more common in older adults.
Subclinical hyperthyroidism is present in approximately 2% of older adults without known thyroid disease. In patients with a TSH <0.1 mIU/L, 1%–2% per year develop overt hyperthyroidism, whereas overt disease develops uncommonly in those with TSH levels between 0.1 – 0.45 mIU/L. TSH normalizes over time in many of these patients, although persistence of subclinical hyperthyroidism is the most common outcome.
Subclinical hyperthyroidism is associated with AF, reduced bone mineral density and increased risk of non-vertebral fractures even in people with thyroid function in the high-normal range. Neuropsychiatric problems including dementia, and excess cardiovascular and all-cause mortality have been reported in some but not all studies.
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12. POTENTIAL FOR CONFUSION IN DIAGNOSING HYPERTHYROIDISM
Many older patients with hyperthyroidism may not have increased T4 levels, despite suppressed TSH
T3 thyrotoxicosis
T3 elevated, T4 level normal
Occurs in a minority of hyperthyroid patients but is more common with aging
High T4 syndrome
Occurs in euthyroid patients with conditions or medications that cause elevated T4 level
TSH level normal
A TSH is an appropriate initial test for hyperthyroidism in relatively healthy older adults, but the diagnosis should be confirmed with a free T4 test. Most asymptomatic older adults with low TSH levels are clinically euthyroid and have normal T4 and T3 concentrations, with normal TSH on repeat testing 4–6 weeks later.
T3 thyrotoxicosis is especially common in patients with toxic adenomas or toxic multinodular goiter.
The high T4 syndrome may occur with drugs or nonthyroidal illnesses that decrease T4-to-T3 conversion (high-dose glucocorticoids or β- blocking agents, acute fasting) or that increase circulating levels of thyroid-binding globulin (estrogens, clofibrate, hepatitis).
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13. TREATMENT OF HYPERTHYROIDISM
Radioactive iodine (RAI) is indicated for most older adults with Graves disease or toxic nodular thyroid disease
For toxic multinodular goiter, higher or repeated doses are often necessary
Antithyroid drugs may be given instead of RAI, or before RAI to control symptoms and avoid worsening of thyrotoxicosis due to release of thyroid hormone after RAI
After RAI, measure serial TSH levels for eventual development of hypothyroidism, or persistent or recurrent hyperthyroidism
Treatment of hyperthyroidism should be considered in older adults with TSH <0.1 mIU/L due to Graves or nodular thyroid disease. Evidence is insufficient to recommend treating older adults with TSH levels between 0.1 and 0.45 mIU/L, although treatment consideration has been advocated based on increased risk of AF in this group.
β-Blocking agents are helpful to manage symptoms such as tachycardia, tremor, and anxiety in patients being treated for hyperthyroidism, but monitor for changes in cardiopulmonary function.
With resolution of hyperthyroidism, the clearance rate of other drugs may decrease, necessitating dosage adjustments to avoid excessive drug levels.
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14. NODULAR THYROID DISEASE
Women ≥70
Incidence of multinodular goiter  with aging
Thyroid nodules present in:
~90% of women ≥70
60% of men ≥80
Most thyroid nodules are nonpalpable
Most nodules are benign, but solitary nodules more often malignant in people ≥60
Men ≥80
Most thyroid nodules are nonpalpable but are detected incidentally on highly sensitive ultrasound or imaging studies done for other reasons. Most thyroid nodules are benign, but they are more likely to be malignant in people ≥60 yr old, especially men. Thyroid cancer is present in 4% to 6.5% of thyroid nodules, and incidentally discovered nonpalpable nodules are as likely to be malignant as palpable nodules.
Multinodular goiters often have autonomously functioning areas, so administration of exogenous thyroid hormone to suppress these goiters may cause iatrogenic hyperthyroidism. Older people with multinodular goiter may develop iodine-induced thyrotoxicosis after receiving radiocontrast or amiodarone.
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15. INDICATIONS FOR THYROID ULTRASONOGRAPHY
Screening
History of head and neck irradiation
Multiple endocrine neoplasia type 2
Family history of thyroid cancer
Diagnosis
Unexplained cervical lymphadenopathy
Guidance for fine-needle aspiration of thyroid nodule(s)
Solitary or dominant nodules, especially if there are characteristics suggesting cancer
Thyroid nodule discovered incidentally on CT, MRI, or 18FDG-PET scanning
Ultrasound is the most sensitive test to detect thyroid nodules. Screening ultrasonography of the thyroid is not indicated in the general population. The procedure should be performed when there is unexplained cervical lymphadenopathy or when risk factors for thyroid cancer are present.
Additionally, ultrasound is warranted in patients with normal or high thyrotropin concentrations and one or more palpable thyroid nodules. However, autonomously functioning thyroid nodules are rarely malignant, so no further evaluation for cancer is required in patients with low thyrotropin concentrations and a “hot” nodule on radionuclide thyroid scanning that corresponds to a palpable nodule.
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16. LEVOTHYROXINE SUPPRESSIVE THERAPY IN THYROID CANCER PATIENTS
Indicated to reduce the risk of cancer recurrence and mortality after total/near-total thyroidectomy
Osteoporosis or adverse effects on heart may occur with long-term thyroid suppression
β-Blockers, bone antiresorptive agents may be useful to minimize these effects
TSH should be suppressed to <0.1 mU/L for high-risk patients with thyroid cancer (>45 years old, large tumor [>4 cm], extrathyroidal extension [capsular and blood vessel invasion], regional lymph node metastasis, or distant metastases, while a lesser degree of thyrotropin suppression at or slightly below normal (0.3–2.0 mU/L) is appropriate for low-risk patients.
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17. DISORDERS OF PARATHYROID AND CALCIUM METABOLISM
Circulating levels of parathyroid hormone (PTH) increase 30% between ages 30 and 80
Despite changes in several systems that regulate calcium homeostasis, serum calcium levels remain normal due to increased PTH
The balance between bone resorption and bone formation is altered in favor of resorption
GRS8 Table 61.2 lists age-related alterations in calcium homeostasis.
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18. VITAMIN D DEFICIENCY
Biochemical marker: circulating 25(OH)D level < 20ng/mL
Affects 20%100% of older community-dwelling adults
Associated with:
Muscle weakness  fall risk
Secondary hyperparathyroidism  increased bone turnover and bone loss
Some studies suggest that vitamin D supplementation >400 IU/day may reduce fracture risk
Optimal 25(OH)D levels for outcomes other than bone health have not been established
25(OH)D = 25-hydroxyvitamin D
Dietary calcium intake is inadequate in most older people, and older people are less able than younger adults to compensate by increasing their intestinal absorption of ingested calcium.
Severe vitamin D deficiency is associated with proximal muscle weakness, myalgias and gait impairment.
Some studies of vitamin D and fracture risk found that vitamin D supplementation at doses sufficient to achieve 25(OH)D levels of 28 to 40 ng/mL was necessary to minimize fracture risk (levels reached only in trials giving 700800 IU/day of vitamin D3). A recent meta-analysis of 12 double-blind RCTs for non-vertebral fractures and 8 RCTs for hip fractures comparing vitamin D with or without calcium supplementation vs. calcium or placebo found a pooled RR of (95% CI, 0.77–0.96) for prevention of non-vertebral fractures and (95% CI, 0.78–1.05) for hip fracture prevention. The effect on fracture reduction was seen only at vitamin D doses > 400 IU/day, which reduced non-vertebral fractures by 29% in community-dwelling older adults and 15% in institutionalized older people. Furthermore, reduction of non-vertebral fractures was found only when vitamin D supplementation was sufficient to achieve 25(OH)D levels ≥ 30 ng/mL.
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19. VITAMIN D DEFICIENCY
Population screening not recommended in current guidelines
Obtain 25(OH)D levels, if available and affordable, in older adults at high risk of vitamin D deficiency:
Obese
History of falls
Nontraumatic fractures
Osteoporosis
Use of anti-epileptic drugs
1,25(OH)2D3 levels not useful except in late-stage chronic kidney disease
Measurements of 1,25(OH)2D3, the active metabolite of vitamin D, are not useful to assess vitamin D status in most individuals because levels are normal or increased in vitamin D-deficient individuals with secondary hyperparathyroidism.
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20. VITAMIN D SUPPLEMENTATION: HOW MUCH IS ENOUGH?
Older adults at risk of falls:
≥800 IU/day of vitamin D
At least 1500–2000 IU/day may be needed to increase 25(OH)D levels to ≥30 ng/mL
Older adults deficient in vitamin D:
50,000 IU/wk of vitamin D2 or D3 for 812 weeks (off-label) until 25(OH)D level > 30 ng/mL
Continue ≥1000–1500 IU/day for maintenance therapy
The USPSTF recommends vitamin D supplementation with 800 IU/day to prevent falls in community-dwelling adults aged 65 years and older who are at increased risk for falls because of a history of recent falls or vitamin D deficiency.
Older people with malabsorption syndromes who are deficient in vitamin D may require vitamin D doses 2- to 3-fold higher, ie, at least –10,000 IU/day of vitamin D to achieve a 25(OH)D level above 30 ng/mL, followed by maintenance therapy of 3000–6000 IU/day.
Maintaining adequate calcium intake (1,000–1,500 mg/day) is also important for bone health and prevention of secondary hyperparathyroidism, although calcium supplementation with or without vitamin D may increase the risk of cardiovascular events.
Unmonitored high-dose vitamin D supplementation may cause vitamin D intoxication (hypercalciuria, hypercalcemia, renal impairment, bone loss).
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Slide 20

21. HYPERCALCEMIA
Most commonly caused by primary hyperparathyroidism (outpatient) or malignancy (hospitalized)
Primary hyperparathyroidism 3 more prevalent in women than in men
Primary hyperparathyroidism is usually asymptomatic
Older adults are more likely than younger adults to have neuropsychiatric symptoms, neuromuscular symptoms, or osteoporosis
Diagnosis of primary hyperparathyroidism is confirmed if PTH is elevated/high normal in presence of hypercalcemia
In hospitalized patients, the most common cause of hypercalcemia is a malignancy that produces PTH-related peptide, with hypercalcemia resulting primarily from increased net bone resorption. The presence of an underlying cancer is usually evident on examination and routine diagnostic testing. Squamous cell cancers of the lung or head and neck are common causes of hypercalcemia due to PTH-related peptide production. Other common malignancies associated with hypercalcemia include breast cancer, lymphoma, and myeloma, although the mechanism of the hypercalcemia is different for many of these cancers.
Acute treatment for malignancy-related hypercalcemia includes volume replacement with intravenous saline, occasionally followed by diuresis with a loop diuretic, but only when rehydration is complete. A parenteral bisphosphonate such as pamidronate or zoledronic acid should be given, along with treatment of the underlying malignancy, if possible. In addition to their usefulness in the treatment of hypercalcemia, bisphosphonates may decrease bone pain and the risk of pathologic fractures in patients with osteolytic bone metastases from a variety of cancers.
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22. DIFFERENTIAL DIAGNOSIS OF HYPERCALCEMIA
Laboratory test
Primary hyper-aparathyroidism
Humoral hypercalcemia of malignancy
Local osteolytic hypercalcemia
Serum calcium 
 or 
Serum phosphate
 or low-normal 
Urine calcium
PTH 
PTH-related peptide
The diagnosis of malignancy-related hypercalcemia is normally straightforward, and extensive diagnostic testing is rarely required.  = increased;  = decreased;  = markedly increased;  = markedly decreased; 0 = undetectable.
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23. TREATMENT OF PRIMARY HYPERPARATHYROIDISM
Surgery for patients with:
Symptomatic primary hyperparathyroidism
No symptoms but serum calcium levels >1 mg/dL above normal
Creatinine clearance <60 mL/min
Markedly decreased bone density
Medical management options:
Alendronate
Cinacalcet in symptomatic patients who are not surgical candidates
Estrogen-progestin therapy
Patients with serum calcium concentrations less than 1 mg/dL above the normal range who are asymptomatic and managed conservatively should avoid lithium carbonate, thiazide diuretics, volume depletion, and immobilization.
Baseline assessment in these patients should include blood pressure, serum calcium phosphate and creatinine, creatinine clearance, and bone densitometry. Follow-up assessments should include serum creatinine and serum calcium every 12 months, and bone densitometry (at 3 sites) every 12 to 24 months. In addition, these patients should be followed clinically for the development of nephrolithiasis, minimal trauma fractures, and neuropsychiatric or neuromuscular symptoms.
Cinacalcet (off-label), a calcimimetic agent that inhibits parathyroid cell function, reduces or normalizes serum calcium levels and reduces PTH levels during long-term treatment of primary hyperparathyroidism, but bone mineral density is not increased. Accordingly, the role of cinacalcet is limited to the management of symptomatic hypercalcemia in patients who are not candidates for parathyroid surgery.
Estrogen-progestin therapy increases bone mineral density in postmenopausal women with primary hyperparathyroidism, but it should not be used as first-line medical therapy because of its associations with increased risk of coronary heart disease, breast cancer, and stroke.
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24. PAGET DISEASE OF BONE
Localized areas of  bone remodeling  change in bone architecture,  tendency to deformity and fracture
Usually asymptomatic
Pain is most common presenting symptom
Bisphosphonates are the treatment of choice; effective for bone pain associated with Paget disease
Parameters to follow during treatment include:
Changes in bone pain, joint function, neurologic status
Serum alkaline phosphatase
The prevalence of Paget disease increases with aging, and it affects 2% to 5% of people aged 50 years and over.
Paget disease is often diagnosed as an incidental finding on radiographs or during evaluation for an unexplained elevation in serum alkaline phosphatase. The most commonly affected sites are the pelvis, spine, femur, tibia, and skull. When Paget disease is symptomatic, pain is the most common presenting symptom, either localized to the affected bones or resulting from secondary osteoarthritic changes, often in the hips, knees, and vertebrae.
When bone deformities occur, the long bones of the lower extremities are usually affected, often with a bowing of the involved extremity. Skull involvement may result in compression of the eighth cranial nerve and sensorineural hearing loss. The most devastating complication of the disease is malignant transformation of the affected bone, especially osteosarcoma.
Treatment is not usually necessary for asymptomatic disease, unless there is concern about hearing loss from skull involvement, nerve root or spinal cord compression from vertebral involvement, or hip fracture from femoral neck involvement. Bisphosphonates suppress the accelerated bone turnover and bone remodeling that is characteristic of this disease.
The main indication for treatment in asymptomatic patients is active disease in areas where complications may occur, including skull, weight-bearing bones, and bone adjacent to major joints, which may increase the risk of secondary osteoarthritis.
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25. HORMONAL REGULATION OF WATER AND ELECTROLYTE BALANCE
Older adults are predisposed to volume depletion and free water excess, due to alterations in:
Total body water content
Secretion of antidiuretic hormone
Osmoreceptor and baroreceptor systems
Urine-concentrating capability
Renal hormone responsiveness
Thirst sensation
Antidiuretic hormone (ADH) secretion tends to be excessive in older people. This state, together with the common occurrence of renal insufficiency, heart failure, hypothyroidism, and diuretic use, predisposes older adults to hyponatremia by impairing free water clearance.
The syndrome of inappropriate antidiuretic hormone (SIADH) is the most common cause of hyponatremia in older adults. Even when mild and apparently asymptomatic, hyponatremia is associated with deficits in gait and attention, falls, and increased fracture risk in older adults.
Medications causing SIADH include the selective serotonin-reuptake inhibitors, sulfonylureas, carbamazepine, oxcarbazepine, and tricyclic antidepressants.
With aging, basal aldosterone secretion declines disproportionately to the decrease in clearance, and atrial natriuretic hormone secretion increases. Atrial natriuretic hormone inhibits aldosterone production and causes natriuresis and diuresis through its effects on the kidneys. Taken together, these changes predispose older people to volume depletion by decreasing the ability of the kidneys to conserve sodium under conditions of fluid deprivation. Baroreceptor ADH responses to hypotension and hypovolemia are decreased in older people, placing them at additional risk of dehydration. Moreover, renal responsiveness to ADH is decreased with aging, resulting in a decreased ability of the kidneys to maximally concentrate urine. Finally, even healthy older adults have decreased thirst sensation and may not be aware that they are becoming dehydrated.
Age-related hyporeninemic hypoaldosteronism also increases the risk of hyperkalemia, especially in patients with diabetes or renal insufficiency. Use of ACE inhibitors, NSAIDs, β-blocking agents, and diuretics with aldosterone-antagonist properties may lead to potentially lethal hyperkalemia in some of these patients.
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26. INTRODUCTION TO DISORDERS OF THE ADRENAL CORTEX
With aging:
 Cortisol secretion is balanced by  clearance
ACTH stimulation of cortisol production is unchanged
Cortisol and ACTH responses are unimpaired
Acute cortisol responses may be higher, more prolonged
Unless emergent, adrenal function testing should be deferred until ≥48 hours after major stressors such as trauma, surgery
Endocrinology consultation if ACTH stimulation test is normal but adrenal insufficiency is suspected
ACTH = adrenocorticotropic hormone
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27. HYPOADRENOCORTICOIDISM
Symptoms are often nonspecific; hyperkalemia may not be present
Most commonly caused by chronic glucocorticoid therapy
Taper the replacement regimen gradually
Give stress dose coverage for acute stressors such as surgery until adrenocortical function has normalized
Recovery is variable, may take several months
Chronic glucocorticoid therapy is the most common cause of adrenal failure in older adults, because of chronic suppression of adrenal function. Autoimmune-mediated adrenal failure is less common in older than in younger adults, but tuberculosis, adrenal metastases, and adrenal hemorrhage in anticoagulated patients are more common causes of adrenal insufficiency in older people.
Older patients with chronic adrenal insufficiency may present with nonspecific symptoms such as anorexia, weight loss, or impaired functional status, and hyponatremia and hyperkalemia may not be present. Accordingly, a high index of suspicion is required to make the diagnosis.
When adrenocortical insufficiency is suspected, the ACTH stimulation test should be performed and therapy initiated. A normal serum cortisol response 30 or 60 min after administration of 250 mcg of ACTH (cosyntropin) is 18 to 20 mcg/dL. A serum ACTH concentration should be obtained before administration of cosyntropin to distinguish secondary adrenal insufficiency (decreased pituitary ACTH secretion), which is characterized by a low or normal ACTH concentration, from primary adrenal insufficiency, which is associated with a high ACTH concentration.
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28. HYPERADRENOCORTICOIDISM
Glucocorticoid therapy is the most common cause of Cushing syndrome in older adults
Adverse effects include psychiatric and cognitive symptoms, osteoporosis, myopathy, and glucose intolerance
Patients beginning long-term glucocorticoid therapy should have:
Baseline and follow-up bone densitometry
Calcium, vitamin D, and antiresorptive treatments such as bisphosphonates as appropriate
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29. ADRENAL NEOPLASMS
Prevalence of adrenal incidentalomas (clinically inapparent adrenal masses) in autopsy studies:
≥10% of older adults
<1% of people <30 years
Most adrenal incidentalomas are benign adrenocortical adenomas
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30. EVALUATING AN ADRENAL INCIDENTALOMA
Diagnosis
Test
Indications
Functional adrenocortical adenoma
24-hour urine free cortisol
1 mg overnight dexamethasone suppression test
Cushing syndrome manifestations
Before major surgery
Pheochromocytoma
24-hour urine metanephrines and catecholamines
Plasma metanephrines
All patients with incidentaloma
Primary aldosteronism
Serum potassium
Ratio of morning plasma aldosterone concentration to plasma renin activity
Hypertension
Hypokalemia
The goals of assessing an adrenal incidentaloma are to determine whether the tumor is functional (hormone-secreting), and whether it is benign or malignant.
Screening for subclinical glucocorticoid hypersecretion is controversial. Many adrenocortical adenomas have a degree of functional autonomy, and some patients may be at increased risk of new vertebral fractures and develop hypertension, insulin resistance, and other metabolic derangements. However, it is unclear whether subclinical glucocorticoid hypersecretion is associated with long-term morbidity, or whether adrenalectomy or medical management of metabolic derangements improves outcomes. Moreover, screening all older adults with adrenal incidentalomas for glucocorticoid hypersecretion would yield a high proportion of false-positive results.
Accordingly, it may be prudent to limit testing to patients with a symptom complex suggesting Cushing syndrome and patients scheduled for major surgery who are at risk of postoperative adrenal crisis.
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31. MALIGNANCY RISK WITH ADRENAL INCIDENTALOMA
Prevalence of adrenal cortical carcinoma in patients with adrenal incidentaloma:
25% of lesions >6 cm
2% of lesions <4 cm
The assessment of malignancy risk in patients with an adrenal incidentaloma is based on the size of the lesion, its imaging characteristics, and its rate of growth.
The individual’s treatment preferences and clinical condition must be taken into account before recommending treatment.
Some experts suggest removal of masses >4 cm; however, the size threshold clearly indicating malignancy is unknown. Patients followed expectantly for masses >2 cm without clearly benign features should receive repeat imaging in 3 to 6 months to identify rapidly growing tumors that are more likely to be malignant.
No size threshold clearly indicates malignancy
Surgical excision generally recommended for masses with high density, irregular shape; unilaterality; tumor calcification; rapid growth
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32. DHEA SUPPLEMENTATION Circulating DHEA levels: Decline with aging
Are associated with poor health
Are positively correlated with some measures of longevity and functional status
Efficacy and safety of DHEA supplementation have not been established
Use of DHEA is inappropriate outside clinical trials
In contrast to cortisol, circulating levels of the principal adrenal androgen, dehydroepiandrosterone (DHEA), decline progressively with aging and in octogenarians are only 10% to 20% of young adult levels.
Most studies involving physiologic to mildly supraphysiologic DHEA supplementation in middle-aged and older adults have not found clinically meaningful beneficial effects on body composition. Although DHEA may increase bone mineral density in postmenopausal women (and not in older men), these effects are minimal in comparison with established treatments for osteoporosis. In RCTs of DHEA supplementation alone for up to 2 yr in older adults with low DHEA concentrations, improvements were not detected in measures of physical performance, well-being, mood, quality of life, and cognition. In one RCT in frail older women, exercise + DHEA supplementation improved some measures of lower- extremity strength and function, but the clinical significance of this finding is unknown.
Potential risks of DHEA treatment include decreased circulating levels of HDL cholesterol in older women, raising the possibility of potential long- term atherogenic effects. Furthermore, DHEA is metabolized to estrogens and to androgens such as testosterone and dihydrotestosterone, and its effects on the risk of breast cancer in women and prostate cancer in men are unknown. Higher dosages of DHEA can cause androgenization in some women and gynecomastia in men.
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33. TESTOSTERONE (T)
Replacement therapy may be considered in older men with ALL of the following:
Total T levels unequivocally well below normal
Severe symptoms of androgen deficiency
No potentially reversible contributing comorbid conditions or medications
More common: low-normal or mildly decreased T levels and nonspecific symptoms such as decreased libido, weakness, decreased muscle mass, osteopenia, and memory loss
T supplementation is hypothesized to be capable of preventing or treating these disorders
Total and free T levels, and T secretion, are lower in healthy older men than in younger men. Many healthy older men exhibit moderate primary testicular failure, with decreased sperm production, testosterone levels, and T secretory responses to gonadotropin administration. Many of these men also have inappropriately normal (ie, not increased) gonadotropin levels in the presence of low T levels, suggesting secondary (hypothalamic or pituitary) testicular failure.
Symptoms suggestive of androgen deficiency include decreased libido, erectile dysfunction, gynecomastia, and hot flushes.
Nonspecific manifestations that may accompany low-normal or mildly decreased serum T levels include decreased libido, weakness, decreased muscle mass, osteopenia or osteoporosis, memory loss, and mild anemia. In most cases, these manifestations have multiple causes, including comorbid conditions and medications. Still, it has been hypothesized that declining T levels with aging contribute to their development.
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34. EVALUATING OLDER MEN WITH SUSPECTED HYPOGONADISM
Serum free or bioavailable T level
LH and FSH levels if abnormally low T level
Baseline bone densitometry
If gonadotropins are low or low-normal, review medications that can suppress gonadotropins and obtain a prolactin level
If prolactin level is high, referral to an endocrinologist and further studies may be warranted, eg, MRI of pituitary fossa, assessment of other pituitary functions
LH = luteinizing hormone; FSH = follicle-stimulating hormone.
Male hypogonadism should be diagnosed only in men with signs and symptoms suggesting androgen deficiency, as well as unequivocally low serum T levels. Men with suspected hypogonadism should be evaluated initially with a morning serum total T level using a reliable assay. The diagnosis should be confirmed by repeating measurement of morning total T, or preferably a morning serum free or bioavailable (non–sex hormone–binding globulin-bound) T level, either measured by equilibrium dialysis or calculated from measurements of total T and sex hormone–binding globulin.
If abnormally low T levels are confirmed, obtain LH and FSH levels to determine whether low T is due to a primary disorder of the testes (primary hypogonadism) or is secondary to a hypothalamic-pituitary disorder (secondary hypogonadism). In addition, consider discontinuing medications that can suppress gonadotropins (eg, glucocorticoids, opioids, and other medications with CNS activity) and obtain a prolactin level if gonadotropins are low-normal or low in the presence of low T levels. High prolactin levels inhibit gonadotropin secretion and could be due to a pituitary adenoma, a hypothalamic disorder, or medications.
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35. TESTOSTERONE SUPPLEMENTATION (1 of 3)
Study end point
Potential short-term effect
Lean body mass
Increased
Fat mass
Decreased
Bone mineral density
Variable: increased at lumbar spine and hip in some studies
Strength
Improved grip strength in some studies
Physical function
Inconsistent effect on leg muscle strength
Inconsistent effects; improved performance of functional tasks in some studies
Sexual function
Variable: activation in sexual behavior and increased libido (most consistent findings)
Mood
Variable: mood and subjective well-being improved in some studies
This table presents data from placebo-controlled studies of T supplementation for up to 3 years in older men with low-normal or mildly decreased serum T levels. The long-term clinical outcomes are unknown. It is also unknown whether the potential benefits and risks are clinically important, or whether the benefits outweigh the risks.
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36. TESTOSTERONE SUPPLEMENTATION (2 of 3)
Study end point
Potential short-term effect
Cognitive
Inconsistent effects: In some studies, some cognitive domains improved (verbal/visual memory, spatial ability, executive function)
Worsened effect of practice on verbal fluency
Lipid profile
Variable: total, LDL, and HDL cholesterol unchanged or decreased
Coronary heart disease
In men with established disease, improved ECG evidence of exercise-induced coronary ischemia (in most studies)
Variable effect on angina pectoris
May  risk CV events in older men with extensive CVD
Prostate
PSA increased slightly in many patients
 incidence of prostate biopsy and prostate cancer dx
Hematocrit
Increased 2.5%–5% vs. baseline
LDL = low-density lipoprotein; HDL = high-density lipoprotein; PSA = prostate-specific antigen.
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37. TESTOSTERONE SUPPLEMENTATION (3 of 3)
Trial of T therapy (off-label) may be appropriate in older men who have serum total T levels <2.8 ng/mL and clinical features suggesting hypogonadism
Monitor patient closely for adverse androgenic effects, including erythrocytosis and potential exacerbation of prostatic disease
There is no direct evidence that T therapy increases the risk of prostate cancer or symptomatic BPH
BPH = benign prostatic hyperplasia
Clinicians should aim to achieve total T levels in the lower part of the normal range for young men (eg, 4–5 ng/mL).
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38. T PREPARATIONS AVAILABLE IN THE US FOR HYPOGONADAL OLDER MEN
Usual treatment dosage
Testosterone enanthate or cypionate
75 mg IM every week, or 150 mg IM every 2 weeks
Non-scrotal transdermal patch
2 or 4 mg transdermal every night
Gel
1% gel: 50–100 mg transdermal every day
1.62% gel: 40.5–81 mg every day
2% gel: 40–70 mg every day
Buccal tablet
30 mg applied to buccal mucosa q12h
Testosterone pellets
150–450 mcg SC every 3–6 months
Solution
30–120 mg applied to axilla once daily
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39. ESTROGEN REPLACEMENT THERAPY (ERT)
Once was standard care for postmenopausal women
Now largely limited to treatment of menopausal symptoms, with or without progesterone
Epidemiologic studies demonstrated reduction in heart disease, but the results of RCTs either have not confirmed this or suggest increased coronary risk
Controlled studies demonstrate either no benefit or detrimental effects with regard to cognitive impairment and dementia
Three meta-analyses of observational studies have demonstrated an association of estrogen therapy in women with a reduction in heart disease by half. However, a few long-term prospective studies of secondary prevention demonstrated increased mortality in the first year on therapy, with improved survival in years 2 through 5, leading to no net benefit. In another trial of women with coronary artery disease, no benefit was found from estrogen for angiographic changes of atherosclerosis.
The Women’s Health Initiative (WHI) is a set of clinical trials to test primary prevention of coronary artery disease with estrogen and estrogen- progesterone combinations. The estrogen-progesterone arm was discontinued early because of the increased risk of coronary disease, breast cancer, stroke, and deep-vein thrombosis; the estrogen-alone arm of the study was discontinued because of increased risk of stroke. Post-hoc analysis of the WHI data suggested that the risk of cardiovascular events was increased in older women and with increased years since menopause.
Although observational studies also suggested that estrogen may have a role in preventing dementia, a placebo-controlled trial of estrogen replacement given for 1 year to 120 women with early to moderate Alzheimer dementia found no improvement in affective or cognitive outcomes. In the WHI, in a study to assess primary prevention, women in the estrogen arm had clinically important declines in their Mini–Mental State Examination scores or transition to mild cognitive impairment or dementia.
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40. Thromboembolic disease
RISKS OF ERT
Breast cancer
Endometrial cancer
Thromboembolic disease
The risks of breast cancer, endometrial cancer, and deep-vein thrombosis/pulmonary emboli associated with the use of estrogen have been well established; these results were confirmed in the WHI trial.
A recent study to assess change in risk approximately 3 years after the WHI trials were discontinued demonstrated continued increased risk with previous estrogen use due to fatal and nonfatal malignancies. The risk of breast cancer was similar to that in the nontreatment arm at the 3-yr follow-up, and the previously demonstrated beneficial effects on colon cancer had dissipated, but risk of lung cancer was higher than in the nontreatment arm. Overall mortality was similar in the estrogen and placebo groups.
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41. GROWTH HORMONE By age 70 to 80:
50% of adults have no significant GH secretion over 24 hours
40% of adults have levels of insulin-like growth factor 1 comparable to those in GH-deficient children
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42. GROWTH HORMONE SUPPLEMENTATION
Recommended only for older people with established hypothalamic-pituitary disease
In RCTs of older people without hypothalamic-pituitary disease:
No augmentation of improvement in muscle strength achieved with exercise alone
No improvement in functional status
Significant adverse effects were common
Long-term efficacy and safety are unknown
Adults with growth hormone deficiency due to hypothalamic-pituitary disease exhibit decreased muscle strength, lean body mass, and bone density; increased abdominal obesity; unfavorable lipid profiles; and an increased risk of cardiovascular disease. Many of these clinical consequences of growth hormone deficiency improve with growth hormone replacement, but not all studies have demonstrated improvements in muscle strength, and the effects on cardiovascular risk are unknown. Older adults without hypothalamic-pituitary disease have many of the same conditions, which leads to the hypothesis that growth hormone supplementation may have a beneficial effect on these clinically important age-related disorders.
Short-term randomized controlled trials of growth hormone supplementation in older adults have reported increased lean body mass and bone density and decreased fat mass. However, growth hormone was not found to augment improvements in muscle strength achieved with exercise alone, and no improvements in functional status were demonstrated. Furthermore, significant adverse effects were common, including carpal tunnel syndrome, arthralgias, edema, and gynecomastia.
Short-term growth hormone supplementation may improve nitrogen balance in older people with severe illness and catabolic states. However, growth hormone is very expensive, and at present it is not recommended for clinical use in older people who do not have established hypothalamic- pituitary disease.
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43. MELATONIN
Hormone secreted by the pineal gland, thought to be involved in regulation of circadian and seasonal biorhythms
Lay press has touted benefits for insomnia, immune deficiency, cancer, and the aging process itself
May induce sleep in older people with insomnia
Long-term risks and benefits of supplementation have not been established for any indication
Melatonin secretion is inhibited by exposure to light, resulting in a marked circadian variation in circulating melatonin levels. The sedative effects of melatonin suggest a role in sleep induction. Most studies show that plasma melatonin levels decline throughout life after early childhood, but the physiologic significance of this decline in melatonin secretion is unclear.
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44. SUMMARY
Older adults with severe hypothyroidism should have testing to exclude concomitant adrenal insufficiency before receiving thyroid hormone replacement
Vitamin D deficiency contributes to osteoporosis and has been associated with muscle weakness and falls
Malignant causes of hypercalcemia include squamous cell cancers, breast cancer, lymphoma, and myeloma
There is little evidence of long-term benefit from supplementation with growth hormone, testosterone, DHEA, or estrogen in older adults
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45. CASE 1 (1 of 4)
A 66-year-old woman comes to the office to discuss results of a screening bone density scan. The results indicated a T score of −1.5.
History includes celiac sprue, which has caused occasional diarrhea since its diagnosis >20 years ago.
She takes a daily multivitamin that has 400 IU of vitamin D3 and 1200 mg of elemental calcium.
She reports having aches and pains throughout her body. Physical examination is normal.
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46. CASE 1 (2 of 4) Laboratory results: Thyroid function Normal
25(OH)D mcg/L
Ionized calcium mg/dL
Phosphorus mg/dL
Alkaline phosphatase 140 mg/dL
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47. CASE 1 (3 of 4)
Which of the following is the most appropriate next step?
Increase elemental calcium intake to 1500 mg and vitamin D intake to 800 IU.
Measure parathyroid hormone level.
Prescribe a loading dose of oral vitamin D over 4–6 weeks.
Repeat bone density scan in 6 months.
Prescribe a bisphosphonate.
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48. CASE 1 (4 of 4)
Which of the following is the most appropriate next step?
Increase elemental calcium intake to 1500 mg and vitamin D intake to 800 IU.
Measure parathyroid hormone level.
Prescribe a loading dose of oral vitamin D over 4–6 weeks.
Repeat bone density scan in 6 months.
Prescribe a bisphosphonate.
ANSWER: C
This patient’s aches and pains and her alkaline phosphatase, phosphorus, and calcium levels are consistent with vitamin D deficiency. Supplemental vitamin D reduces the risk of bone fractures associated with deficiency; supplementation must be accompanied by adequate amounts of calcium in the diet. In a meta- analysis of 12 randomized, controlled trials of fracture risk in older adults, vitamin D 700–800 IU/day reduced the relative risk of hip fracture by 26% and the relative risk of other nonvertebral fractures by 23% as compared with calcium alone or placebo (number needed to treat=15). Because it is possible that this patient has been malabsorbing vitamin D for many years because of fat malabsorption related to diarrhea, measuring serum levels is the only way to confirm that she has adequate stores of vitamin D after replacement.
There is no reason to suspect hyperparathyroidism, because her serum calcium level is normal. She may benefit from an increase in daily calcium, but she needs adequate amounts of vitamin D to mineralize her bone matrix and to maximally absorb dietary calcium from her GI tract. An increased daily supplemental dosage of vitamin D is not adequate to replenish vitamin D stores. Bisphosphonates are used to treat osteoporosis, not osteomalacia resulting from vitamin D deficiency. She may have osteoporosis and require bisphosphonate treatment to maximize bone mineral density, but treating the vitamin D deficiency is the first step toward improving her bone health.
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49. CASE 2 (1 of 3)
A 77-year-old woman comes to the office for evaluation of fatigue. History includes glaucoma, constipation, hypertension, and hyperlipidemia.
Laboratory studies:
Fasting glucose 90 mg/dL
Hemoglobin g/dL
Total cholesterol 253 mg/dL
Triglycerides 100 mg/dL
Sodium mEq/​L
Potassium mEq/​L
Thyrotropin IU/​mL
Free T ng/dL
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50. Which of the following is the most appropriate next step?
CASE 2 (2 of 3)
Which of the following is the most appropriate next step?
Report to the patient that test results are normal for a person her age.
Obtain CT of pituitary gland to exclude diagnosis of adenoma.
Obtain radioactive iodine scan of thyroid gland.
Prescribe L-thyroxine, 25 mcg daily.
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51. Which of the following is the most appropriate next step?
CASE 2 (3 of 3)
Which of the following is the most appropriate next step?
Report to the patient that test results are normal for a person her age.
Obtain CT of pituitary gland to exclude diagnosis of adenoma.
Obtain radioactive iodine scan of thyroid gland.
Prescribe L-thyroxine, 25 mcg daily.
ANSWER: D
This patient’s increased thyrotropin level and normal free T4 level suggest subclinical hypothyroidism. Reducing the thyrotropin level to within normal range may improve her glaucoma, constipation, and hyperlipidemia; treatment is suggested for asymptomatic patients when the thyrotropin level is >10 IU/​mL. Thyroid hormone replacement should begin with a low dosage of L-thyroxine and then be increased at intervals that correlate with the half-life of thyroxine. In older adults, the half-life may be as long as 9 days. The risk of adverse effects may be reduced by waiting 4–6 weeks to achieve a steady state on a given dose of thyroid hormone before increasing the dosage.
An increased thyrotropin level is not a normal finding regardless of the patient’s age. Radioactive iodine scan offers little clinical benefit and is not recommended. There is no evidence of a thyrotropin-secreting pituitary adenoma, which is extremely rare.
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52. CASE 3 (1 of 4)
A 70-year-old woman comes to the office for a follow-up visit. Last week she went to the local emergency department because she had abdominal pain and diarrhea for >24 hours; while there, she underwent CT of the abdomen.
The ED physician diagnosed a viral illness.
The abdominal symptoms have resolved, and she reports no change in her overall health.
History includes hypertension controlled with hydrochlorothiazide.
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53. CASE 3 (2 of 4) On physical examination, all findings are normal.
The final CT report is now available and refers to the presence of a 2.5-cm left adrenal mass.
Electrolyte, blood sugar, and fractionated plasma metanephrine levels are normal, as are results of an overnight dexamethasone suppression test.
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54. CASE 3 (3 of 4)
Which of the following is the most appropriate next step?
Refer the patient to a surgeon for removal of the adrenal mass.
Refer the patient for fine-needle aspiration biopsy of the adrenal mass.
Obtain MRI.
Schedule repeat CT in 3 months.
Explain to the patient that no follow-up is needed.
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55. CASE 3 (4 of 4)
Which of the following is the most appropriate next step?
Refer the patient to a surgeon for removal of the adrenal mass.
Refer the patient for fine-needle aspiration biopsy of the adrenal mass.
Obtain MRI.
Schedule repeat CT in 3 months.
Explain to the patient that no follow-up is needed.
ANSWER: D
CT should be repeated 3 months after initial discovery for patients who have an adrenal nodule measuring between 2 and 4 cm, or in whom the initial image is suspicious. For patients who have no history of malignancy and who have small (<2 cm), uniform, hypodense cortical nodules suggesting a benign lesion, repeat imaging in 3 to 6 months is reasonable. Current practice is to surgically remove any tumor that enlarges by >1 cm in diameter during the follow-up period or that is >4 cm on initial observation. Glucocorticoid and catecholamine function should be evaluated annually for 4 years in cases in which initial evaluation is negative.
A homogeneous adrenal mass <4 cm in diameter with a smooth border, low attenuation value (<10 HU on unenhanced CT), and rapid contrast medium washout (>50% at 10 minutes) is most likely a benign cortical adenoma. Characteristics suggesting adrenal carcinoma or metastases include irregular shape, diameter >4 cm, inhomogeneous density, high attenuation values (>20 HU on unenhanced CT), delayed contrast medium washout, and tumor calcification.
Pheochromocytoma should be excluded in all patients by measuring 24-hour urine fractionated metanephrine and catecholamine levels or plasma fractionated metanephrine levels. Subclinical Cushing syndrome should be excluded with the 1- mg overnight dexamethasone suppression test. In patients with hypertension, primary aldosteronism should be excluded by calculation of the plasma aldosterone to plasma renin activity ratio and plasma potassium concentration.
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56. Copyright © 2013 American Geriatrics Society
GRS8 Slides Editor: Annette Medina-Walpole, MD, AGSF GRS8 Chapter Authors: David A. Gruenewald, MD Anne M. Kenny, MD Alvin M. Matsumoto, MD GRS8 Question Writer: Steven R. Gambert, MD, ACP, AGSF Medical Writers: Beverly A. Caley Faith Reidenbach Managing Editor: Andrea N. Sherman, MS
Copyright © 2013 American Geriatrics Society
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