Download GRS8EndocrineMetabolicDisorders

1
ENDOCRINE AND
METABOLIC
DISORDERS
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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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TO P I C S C O V E R E D
• 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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H O M E O S TAT I C R E G U L AT I O N
• 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
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
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I N T R O D U C T I O N 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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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
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
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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
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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
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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
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
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T R E AT M E N T O F
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
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NODULAR THYROID DISEASE
• Incidence of multinodular goiter 
with aging
Women ≥70
• 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
Present
Not Present
Men ≥80
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
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LEVOTHYROXINE SUPPRESSIVE THERAPY
I N T H Y R O I D C A N C E R PAT I E N T S
• 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
D I S O R D E R S O F PA R AT H Y R O I D A N D
C A L C I U M M E TA B O L I S M
• 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
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V I TA M I N D D E F I C I E N C Y
• 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
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V I TA M I N D D E F I C I E N C Y
• 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
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
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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
DIFFERENTIAL DIAGNOSIS OF
HYPERCALCEMIA
Primary hyperaparathyroidism
Humoral
hypercalcemia
of malignancy
Local osteolytic
hypercalcemia

 or 
 or 
 or low-normal


Urine calcium



PTH



PTH-related
peptide
0

0
Laboratory test
Serum calcium
Serum
phosphate
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T R E AT M E N T O F P R I M A RY
H Y P E R PA R AT H Y R O I D I S M
• 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
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PA G E T D I S E A S E O F B O N E
• 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
H O R M O N A L R E G U L AT I O N O F WAT E R
A N D E L E C T R O LY T E B A L A N C E
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
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I N T R O D U C T I O N TO D I S O R D E R S
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
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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
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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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ADRENAL NEOPLASMS
• Prevalence of adrenal incidentalomas (clinically
inapparent adrenal masses) in autopsy studies:
≥10% of older
adults
12%
10%
8%
6%
4%
<1% of people <30 years
2%
0%
• Most adrenal incidentalomas are benign
adrenocortical adenomas
EVALUATING AN
ADRENAL INCIDENTALOMA
Diagnosis
Test
Functional
• 24-hour urine free cortisol
adrenocortical adenoma • 1 mg overnight
dexamethasone suppression
test
Indications
• Cushing syndrome
manifestations
• Before major
surgery
Pheochromocytoma
• 24-hour urine metanephrines
and catecholamines
• Plasma metanephrines
• All patients with
incidentaloma
• Before major
surgery
Primary aldosteronism
• Serum potassium
• Ratio of morning plasma
aldosterone concentration to
plasma renin activity
• Hypertension
• Hypokalemia
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MALIGNANCY RISK
W I T H A D R E N A L I N C I D E N TA L O M A
• Prevalence of adrenal cortical carcinoma in patients with adrenal
incidentaloma:
30%
25% of lesions >6 cm
25%
20%
15%
10%
5%
2% of lesions <4 cm
0%
• 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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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
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T E S TO S T E R O N E ( 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
E VA L U AT I N G O L D E R M E N W I T H
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
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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
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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
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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
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T PREPARATIONS AVAILABLE IN THE US
FOR HYPOGONADAL OLDER MEN
Preparation
Testosterone enanthate or
cypionate
Usual treatment dosage
• 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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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
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RISKS OF ERT
• Breast cancer
• Endometrial cancer
• Thromboembolic disease
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GROWTH HORMONE
By age 70 to 80:
• 50% of adults have no
significant GH secretion
over 24 hours
Virtually Absent
Less Affected
• 40% of adults have levels
of insulin-like growth
factor 1 comparable to
those in GH-deficient
children
Low
Normal
GROWTH HORMONE
S U P P L E M E N TAT I O N
• 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
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M E L ATO N I N
• 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
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S U M M A RY
• 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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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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CASE 1 (2 of 4)
Laboratory results:
•
•
•
•
•
Thyroid function
25(OH)D
Ionized calcium
Phosphorus
Alkaline phosphatase
Normal
8 mcg/L
4.0 mg/dL
2.0 mg/dL
140 mg/dL
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CASE 1 (3 of 4)
Which of the following is the most appropriate next step?
A. Increase elemental calcium intake to 1500 mg and
vitamin D intake to 800 IU.
B. Measure parathyroid hormone level.
C. Prescribe a loading dose of oral vitamin D over 4–6
weeks.
D. Repeat bone density scan in 6 months.
E. Prescribe a bisphosphonate.
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CASE 1 (4 of 4)
Which of the following is the most appropriate next step?
A. Increase elemental calcium intake to 1500 mg and
vitamin D intake to 800 IU.
B. Measure parathyroid hormone level.
C. Prescribe a loading dose of oral vitamin D over 4–6
weeks.
D. Repeat bone density scan in 6 months.
E. Prescribe a bisphosphonate.
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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
Hemoglobin
Total cholesterol
Triglycerides
Sodium
Potassium
Thyrotropin
Free T4
90 mg/dL
13.6 g/dL
253 mg/dL
100 mg/dL
142 mEq/​L
4.0 mEq/​L
20.0 IU/​mL
0.6 ng/dL
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CASE 2 (2 of 3)
Which of the following is the most appropriate next
step?
A. Report to the patient that test results are
normal for a person her age.
B. Obtain CT of pituitary gland to exclude
diagnosis of adenoma.
C. Obtain radioactive iodine scan of thyroid gland.
D. Prescribe L-thyroxine, 25 mcg daily.
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CASE 2 (3 of 3)
Which of the following is the most appropriate next
step?
A. Report to the patient that test results are
normal for a person her age.
B. Obtain CT of pituitary gland to exclude
diagnosis of adenoma.
C. Obtain radioactive iodine scan of thyroid gland.
D. Prescribe L-thyroxine, 25 mcg daily.
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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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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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CASE 3 (3 of 4)
Which of the following is the most appropriate next step?
A. Refer the patient to a surgeon for removal of the
adrenal mass.
B. Refer the patient for fine-needle aspiration biopsy of
the adrenal mass.
C. Obtain MRI.
D. Schedule repeat CT in 3 months.
E. Explain to the patient that no follow-up is needed.
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CASE 3 (4 of 4)
Which of the following is the most appropriate next step?
A. Refer the patient to a surgeon for removal of the
adrenal mass.
B. Refer the patient for fine-needle aspiration biopsy of
the adrenal mass.
C. Obtain MRI.
D. Schedule repeat CT in 3 months.
E. Explain to the patient that no follow-up is needed.
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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