Download Endocrinology.GRS9 - Geriatrics Care Online

1
ENDOCRINOLOGY
2
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
3
TOPICS COVERED
• Thyroid Disorders
• Disorders of Parathyroid and Calcium Metabolism
• Disorders of the Anterior Pituitary
• Disorders of the Adrenal Cortex
• Testosterone
• Estrogen Therapy
• Growth Hormone
• Melatonin
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
changes in catabolism that maintain
homeostasis
• In some instances, compensatory changes in
hormone catabolism do not fully offset agerelated impairment in endocrine functions
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 many lab tests, normal ranges for healthy
older people are not available
5
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 thyrotropin concentration shifts towards a
higher level  contributing to the 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
6
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
 Epidemiologic studies in older adults have not
found a consistent association between
subclinical hypothyroidism and risk of coronary
heart disease mortality or total mortality
POTENTIAL FOR CONFUSION IN
DIAGNOSING HYPOTHYROIDISM
• Nonthyroidal illness
 Low T4 syndrome: Low serum total T4, free T4 usually
normal without increased TSH level in euthyroid patients
with severe nonthyroidal illnesses.
 Low T3 syndrome: Most common alteration in thyroid
hormone levels in nonthyroidal illness, occurring in even
mild nonthyroidal illnesses
• Secondary hypothyroidism
 Inappropriately normal or low TSH, low free T4 level
 Decreased reverse T3
 Hypopituitarism
8
MANAGEMENT OF
SUBCLINICAL HYPOTHYROIDISM
Consider T4 replacement in older adults with TSH
persistently >10 mIU/L
• T4 supplementation in older people with mild
elevation in TSH may be of limited benefit or even
harmful
• If not treated with T4: monitor TSH, free T4 every 6
months until stable, then yearly
9
10
T4 REPLACEMENT
• Usually started at low dosage (eg, 25 mcg/day) and
increased every 4–6 weeks until TSH normal
• In patients with severe 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 to avoid precipitating an
adrenal crisis
 Start at 50 to 100 mcg/day, or up to 200 mcg IV followed by
100 mcg IV daily until oral intake is possible for patients with
myxedema stupor or coma, even with a history of cardiac
disease
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 anorexia, weight loss, constipation,
muscle weakness, or cardiac symptoms
POTENTIAL FOR CONFUSION IN
DIAGNOSING HYPERTHYROIDISM
• Most asymptomatic older adults with low TSH are
clinically euthyroid with normal T4 and T3, and TSH
might be normal on repeat testing 4-6 weeks later
• 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 nonthyroidal illness
or medications that cause elevated T4 level
 TSH level normal
12
13
SUBCLINICAL HYPERTHYROIDISM
• Low or undetectable serum TSH with normal free T4 and
T3 levels, present in 2% of older adults without known
thyroid disease
• Associated with AF in those with TSH <0.45 mIU/L,
especially if TSH <0.1 mIU/L, as well as in people with
thyroid function in the high-normal range
• Can accelerate bone mineral density loss
• Low TSH shown to be associated with cognitive
impairment and dementia; it is unknown whether
antithyroid therapy can prevent cognitive decline in these
individuals
TREATMENT OF
HYPERTHYROIDISM
• Radioactive iodine (RAI) is the treatment of choice 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 before RAI, to control
symptoms and avoid worsening of thyrotoxicosis due to
release of thyroid hormone after RAI
• After RAI, measure serial TSH levels to monitor for
eventual development of hypothyroidism, or persistent or
recurrent hyperthyroidism
14
15
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
• Selection of thyroid nodule(s) for biopsy
• Guidance for fine-needle aspiration of single or multiple
thyroid nodule(s)
• Identification of nodular characteristics suspicious for
cancer
• Thyroid nodule discovered incidentally on CT, MRI, or
PET scanning
16
17
THYROID NODULES
• Autonomously functioning thyroid nodules are
rarely malignant
• A nonfunctioning (“cold”) nodule requires FNA to
exclude malignancy
• In general, nodules >1 cm require evaluation for
malignancy
18
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
DISORDERS OF PARATHYROID AND
CALCIUM METABOLISM
• Circulating levels of parathyroid hormone (PTH)
increase 30% between ages 30 and 80
• Serum calcium levels remain normal due to
increased PTH
• The balance between bone resorption and
bone formation is altered in favor of resorption
• Results in decreased bone mass and increased
risk of osteoporosis
19
20
VITAMIN D DEFICIENCY (1 of 2)
• Defined as circulating 25(OH)D level < 20ng/mL
• Very common; affects 26.6% of men, 33.6% of
women of all races >70 years old
• Exposure to natural sunlight is the major source of
vitamin D
 Even with adequate exposure to sunlight, the synthesis of
vitamin D in skin declines progressively with aging
• Associated with:
 Muscle weakness  fall risk
 Secondary hyperparathyroidism  increased bone turnover
and bone loss
21
VITAMIN D DEFICIENCY (2 of 2)
• Population screening not recommended in current
guidelines
• Obtain 25(OH)D levels in older adults at high risk of
vitamin D deficiency:






Obese
Malnourished or losing weight
History of falls
Nontraumatic fractures
Osteoporosis
Use of anti-epileptic drugs or corticosteroids
• 1,25(OH)2D3 levels not useful except in late-stage
chronic kidney disease
22
OPTIMAL VITAMIN D LEVELS
• Institute of Medicine (IOM) in 2010 recommended
25(OH)D be >20 ng/mL
 There is general agreement that 25(OH)D <20 ng/mL is
suboptimal for bone health
 Optimal concentrations for other outcomes have not been
established
• American Geriatrics Society (AGS) Workgroup on
Vitamin D Supplementation for Older Adults advocate
minimum level of 30 ng/mL in older adults
 25(OH)D <30 ng/mL are associated with impaired balance
and LE function, muscle weakness, decreased BMD, and
increased fall rates
 >75% of older adults in the US have levels <30 ng/mL
VITAMIN D SUPPLEMENTATION:
HOW MUCH IS ENOUGH?
• Daily vitamin D intake
 IOM: 800 IU/d of vitamin D3 in those >70
 AGS: at least 1000 IU/d in older adults, along with
calcium supplementation to reduce risk of falls and
fractures
• High-dose vitamin D supplementation may cause
hypercalciuria, hypercalcemia, impairment of kidney
function, and bone loss
• Vitamin D-deficient older adults should have 50,000
IU/week of vitamin D2OL or D3 for 8-12 weeks (or 6,000
IU daily), followed by 1,000-1,500 IU/d for maintenance
therapy
23
24
HYPERCALCEMIA
• Most commonly caused by primary hyperparathyroidism or
malignancy
• 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,
HTN, or osteoporosis
• Diagnosis of primary hyperparathyroidism is confirmed if
PTH is elevated/high normal in presence of hypercalcemia
DIFFERENTIAL DIAGNOSIS OF
HYPERCALCEMIA
Laboratory test
Primary hyperaparathyroidism
Humoral
hypercalcemia
of malignancy
Local osteolytic
hypercalcemia
Serum calcium

 or 
 or 
 or low-normal


Urine calcium



PTH



PTH-related
peptide
0

0
Serum
phosphate
25
TREATMENT OF PRIMARY
HYPERPARATHYROIDISM (1 of 2)
• Surgery for patients with:
 Symptomatic primary hyperparathyroidism
 No symptoms, but with
 Serum calcium levels >1 mg/dL above normal
 Creatinine clearance <60 mL/min
 Markedly decreased bone density, vertebral fracture,
nephrolithiasis, or nephrocalcinosis on imaging
 Or 24-h urine calcium >400 mg/d with increased stone risk
by biochemical stone risk analysis
26
TREATMENT OF PRIMARY
HYPERPARATHYROIDISM (2 of 2)
• Repletion of vitamin D deficiency may improve some
manifestations of primary hyperparathyroidism such as
reduced BMD and fracture risk
 Replete cautiously due to risk of hypercalcemia and
hypercalciuria (starting dose of 600-1000 IU/d)
• Medical management options:
 Alendronate
 Cinacalcet in symptomatic patients who are not surgical
candidates
 Estrogen-progestin therapy
27
28
HYPERCALCEMIA OF MALIGNANCY
• Most common cause of hypercalcemia in hospitalized
patients
• Presence of an underlying cancer is usually evident
 Squamous cell cancers of the lung or head and neck are
common causes due to production of PTH-related peptide
(PTHrp)
 Breast cancer, lymphoma, and myeloma are common
malignancies associated with hypercalcemia, though usually not
PTHrp related
• Treatment
 Volume replacement with IV saline, parenteral bisphosphonate,
treatment of underlying malignancy if possible
29
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; suppress
the accelerated bone turnover and bone remodeling
• Parameters to follow during treatment include:
 Changes in bone pain, joint function, neurologic status
 Serum alkaline phosphatase or bone-specific alkaline
phosphatase
DISORDERS OF THE
ANTERIOR PITUITARY
• It is challenging to separate the effects of aging on
pituitary hormone secretion from the effects of comorbid
illnesses, medications, body composition, physical
activity, and other confounding factors
• Aging effects on pituitary hormone secretion may only
become evident in response to stimulatory (or inhibitory)
influences, not in the basal state
30
31
ANTERIOR PITUITARY FUNCTION AND CIRULATING
TARGET ORGAN HORMONE LEVELS IN AGING (1 of 5)
Endocrine Parameter
Effect of Aging
Hypothalamic-Pituitary-Thyroid Axis
Thyroxine (T4)
Unchanged
Triiodothyronine (T3)
Decreased, especially if systemic illness
or debilitation
Thyrotropin (TSH)
Unchanged; increased in women
Suppression of TSH by T4
Increased (ie, smaller T4 dose required
to suppress TSH)
32
ANTERIOR PITUITARY FUNCTION AND CIRULATING
TARGET ORGAN HORMONE LEVELS IN AGING (2 of 5)
Endocrine Parameter
Effect of Aging
Hypothalamic-Pituitary-Adrenal Axis
Cortisol
Unchanged
Adrenocorticotropic hormone (ACTH) Unchanged
Diurnal rhythm of cortisol and ACTH Decreased (reduced amplitude
and phase advance of cortisol
variation)
ACTH stimulation of cortisol
Unchanged
Unchanged
Feedback suppression of ACTH by
cortisol
Unchanged; increased (CRH)
Stimulation of ACTH and cortisol by
insulin-induced hypoglycemia,
corticotropin-releasing hormone
(CRH), metyrapone
Recovery of ACTH and cortisol after
stress
Decreased (peak cortisol levels
higher, remain increased
longer)
33
ANTERIOR PITUITARY FUNCTION AND CIRULATING
TARGET ORGAN HORMONE LEVELS IN AGING (3 of 5)
Endocrine Parameter
Effect of Aging
Growth Hormone (GH) Axis
Insulin-like growth factor 1 (IGF-1)
Decreased
GH secretion during sleep
Decreased
GH secretion with fasting and exercise
Decreased
Amplitude of pulsatile GH secretion
Decreased
Frequency of pulsatile GH secretion
Unchanged
Unchanged
GH response to insulin-induced
hypoglycemia
GH response to GH-releasing hormone
Decreased
34
ANTERIOR PITUITARY FUNCTION AND CIRULATING
TARGET ORGAN HORMONE LEVELS IN AGING (4 of 5)
Endocrine Parameter
Effect of Aging
Hypothalamic-Pituitary-Testicular Axis
Total testosterone
Decreased
Markedly decreased
Free and bioavailable
testosterone
Sex hormone binding
Increased (usually within normal range
globulin
until advanced age)
Luteinizing hormone (LH)
Unchanged/increased (usually within
normal range until advanced age)
Follicle-stimulating
Unchanged/increased (may remain
hormone (FSH)
within normal range until advanced age)
Decreased
Frequency of pulsatile LH
secretion
Unchanged
LH response to
gonadotropin-releasing
hormone (GnRH)
35
ANTERIOR PITUITARY FUNCTION AND CIRULATING
TARGET ORGAN HORMONE LEVELS IN AGING (5 of 5)
Endocrine Parameter
Prolactin
Nocturnal prolactin
secretion
Amplitude of pulsatile
prolactin secretion
Effect of Aging
Prolactin
Decreased
Decreased
Decreased
36
HYPERPROLACTINEMIA
• Mild hyperprolactinemia can be caused by renal failure,
primary hypothyroidism, hypothalamic disease that
interfere with synthesis of dopamine, and meds that
inhibit dopamine activity
• Clinical manifestations often subtle and unrecognized
 Sexual dysfunction, gynecomastia, osteoporosis, rarely
galactorrhea
• Workup may include imaging of hypothalamus and
pituitary to exclude a tumor or other lesion
37
TREATMENT OF HYPERPROLACTINEMIA
• Hyperprolactinemia due to a pituitary microadenoma
(<10mm) may be managed with observation if
asymptomatic
• Dopamine agonists are first-line treatment for
hyperprolactinemia from any cause and are effective in
reducing prolactin concentrations
 Possible adverse effects in older adults: hallucinations, GI
symptoms
 Start at low doses and increase slowly
• Trans-sphenoidal surgery or radiation therapy
occasionally necessary in patients with
macroprolactinomas and persistent visual field defects or
who cannot tolerate dopamine agonists
38
PITUITARY ADENOMAS
• Incidence increases with aging, but most remain
asymptomatic
• Most are nonfunctioning adenomas
• Approach to pituitary “incidentalomas” found on imaging
studies
 Perform careful clinical evaluation, measurement of pituitary and
end-organ hormones to exclude hypopituitarism and hormone
hypersecretion, and visual field examination when the tumor is
adjacent to optic chiasm or optic nerves
• Pituitary microadenomas may be managed expectantly
• Macroadenomas other than prolactinomas should be
referred for trans-sphenoidal surgery if there are visual
field abnormalities; hypersecretion of TSH, ACTH, or
GH; or other neurologic symptoms
39
HYPOPITUITARISM
• Develops in 1/3 to 1/2 of older adults with pituitary
tumors
• Also caused by traumatic brain injury (TBI), infections
(eg, TB), metastatic cancer, prior irradiation or surgery
for pituitary tumors, and vascular disorders (eg, pituitary
infarction or carotid artery aneurysms)
• Manifestations of panhypopituitarism: fatigue,
hypogonadism, loss of libido, hypotension, weight loss,
hypoglycemia, hyponatremia
• When diagnosis is suspected, measure pituitary and
target organ hormone levels, including dynamic testing
of the HPA axis with ACTH stimulation testing
40
HYPOPITUITARISM AND TBI
• Hypopituitarism is common after a fall with head injury in
older adults, even with mild TBI
• Potentially life-threatening glucocorticoid insufficiency
may develop in the acute phase of TBI (first 7-10 days)
 Obtain serial morning cortisol measurements especially when
signs such as hypotension, hypoglycemia, and hyponatremia are
present
• After the acute phase, some hormonal deficiencies that
were manifest initially may resolve, and others may
develop
 Monitor for signs and symptoms and obtain hormone
measurements 3-6 months after TBI, again at 1 year, and
annually thereafter, and reevaluate hormonal status whenever
concerning symptoms develop
41
EMPTY SELLA SYNDROME
• Observed in 19% of older subjects
• Pituitary height and volume tend to diminish with aging in
healthy adults
• Increasingly being detected as neuroimaging for other
indications has increased
• Unknown whether it has functional significance when
incidentally found in healthy older adults
• Conservative management is appropriate in these cases,
with visual field testing and pituitary and target organ
hormone measurements to detect abnormalities in
pituitary hormones
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
42
43
HYPOADRENOCORTICOIDISM
• Causes: Chronic glucocorticoid therapy (most common
cause in older adults), autoimmune-mediated adrenal
failure (less common in older than younger adults), TB,
adrenal metastases, adrenal hemorrhage in
anticoagulated patients, prolonged use of megestrol
acetate
• Possible symptoms: anorexia, nausea, weight loss,
abdominal pain, weakness, hypotension, impaired
functional status, hyponatremia and hyperkalemia
• When suspected, the ACTH stimulation test should be
performed, and therapy initiated
44
HYPERADRENOCORTICOIDISM
• Exogenous glucocorticoids are the most common cause
in older adults
• Often causes adverse events: psychiatric and cognitive
symptoms, osteoporosis, myopathy, and glucose
intolerance
• For patients beginning long-term glucocorticoid therapy,
baseline and follow-up bone densitometry
measurements are indicated
 Calcium, vitamin D, and antiresorptive treatments should be
started as appropriate in patients at high risk of fractures
 Hormone replacement therapy may also be appropriate in some
cases to counteract corticosteroid-induced suppression of sex
hormones
45
ADRENAL NEOPLASMS
• Adrenal incidentalomas present in ≥10% of older adults
 Most are benign adrenocortical adenomas, though
pheochromocytomas and adrenocortical carcinomas are
also found
• Goals of assessment:
 Determine whether tumor is functional (hormonesecreting)
 Determine whether tumor is benign or malignant
• Most useful initial tool: attenuation coefficient in
Hounsfield units (HU) on noncontrast CT imaging
• Lesions ≤10 HU, or >10 HU but size <4cm are likely
benign adenomas
ADRENAL INCIDENTALOMAS: EVALUATION OF
HORMONE HYPERSECRETION
Indications
Test and Result Supporting
Diagnosis
Diagnosis
Cushing syndrome
1 mg overnight
manifestations,
dexamethasone suppression
before major surgery test showing failure to
suppress cortisol
24-hour urine free cortisol ↑
Functional
adrenocortical
adenoma
All patients with
incidentaloma
24-hour urine for fractionated
metanephrines ↑ or plasma
free metanephrines ↑
Pheochromocytoma
Before major
surgery
Plasma free metanephrines ↑
Pheochromocytoma
Hypertension with or Ratio of morning plasma
without hypokalemia aldosterone concentration to
plasma renin activity ↑
Primary aldosteronism
46
47
DHEA SUPPLEMENTATION
• Circulating DHEA levels decline with aging
• Low DHEA levels:
 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
• RCTs for up to 2 years have not found clear evidence of clinically
meaningful benefit
• Use of DHEA is inappropriate outside clinical studies
48
TESTOSTERONE (T)
• Age-related male hypogonadism should be diagnosed
only in older men with 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 and potency, reduced energy, depressed mood,
weakness, decreased muscle mass, osteopenia,
metabolic syndrome, and memory loss
 It is unclear whether this situation reflects overall poor health
or represents a T deficiency state warranting treatment
EVALUATING OLDER MEN WITH
SUSPECTED HYPOGONADISM
49
• If symptoms/signs of androgen deficiency, obtain morning
serum free or bioavailable T level
• If low T level, repeat T level and obtain LH and FSH levels
• Baseline bone densitometry, if high fracture risk
• 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
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 effects; improved performance of
functional tasks in some studies
• Improvement more likely in older, frail men in one study
Sexual function
• Variable: most consistent findings are activation in
sexual behavior and increased libido
Mood
• Variable: mood and subjective well-being improved in
some studies
• Inconsistent effects on depression
50
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
Quality of Life
• Inconsistent effects; some studies show significant
improvement of physical function domain and
improvement in subjects with more somatic symptoms at
baseline
Lipid profile
• Variable: total, LDL, and HDL cholesterol unchanged or
decreased
Coronary heart
disease
• May  risk CV events in older men with extensive CVD
and immobility
Prostate
• PSA increased slightly in many men
•  incidence of prostate-related events
Hematocrit
• Increased 2.5%–5% vs. baseline
51
TESTOSTERONE
SUPPLEMENTATION (3 of 3)
• T supplementation should be considered only after
optimizing potentially reversible functional causes of
hypogonadism, eg, stopping medications that may cause
clinical manifestations of hypogonadism
• After discussing risks and benefits, a trial of T therapy (offlabel) may be appropriate in older men with serum total T
levels <2.8 ng/mL and clinical features suggesting
hypogonadism
• Monitor closely for efficacy and adverse events, including
erythrocytosis, lower urinary tract symptoms, new or
worsening snoring or signs of obstructive sleep apnea
syndrome, or gynecomastia
52
T PREPARATIONS AVAILABLE IN THE US
FOR HYPOGONADAL OLDER MEN
Preparation
Initial Treatment Dosage
Testosterone enanthate or
cypionate
• 75 mg IM every week, or 150 mg IM every
2 weeks
Testosterone undecanoate
• 750 mg IM initially, followed by 750 mg IM
4 weeks later, then 750 mg every 10
weeks thereafter
• 2 or 4 mg transdermal every night
Non-scrotal transdermal
patch
Gel
• 1% gel: 25–100 mg transdermal every day
• 1.62% gel: 20.25–81 mg every day
• 2% gel: 10–70 mg every day
Solution
• 30–120 mg applied to axilla once daily
Intranasal gel
• 5.5 mg (1 actuation) each nostril 3 times
daily
Buccal tablet
• 30 mg applied to buccal mucosa q12h
Testosterone pellets
• 150–450 mcg SC every 3–6 months
53
54
ESTROGEN THERAPY
• Replacement of estrogen, with or without progesterone,
once was standard care for postmenopausal women
• Is no longer due to more recent data from RCTs
demonstrating significant adverse events from such
therapy
 Breast cancer, endometrial cancer, DVT/PE, stroke
• Now largely limited to treatment of menopausal
symptoms
• Controlled studies demonstrate either no benefit or
detrimental effects with regard to cognitive impairment
and dementia
55
GROWTH HORMONE (GH)
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
SUPPLEMENTATION
• Not recommended for clinical use in older adults
without 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, bone density, or lipid
levels
 Significant adverse effects were common
• Long-term efficacy and safety are unknown
56
57
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
• Long-term risks and benefits of supplementation
have not been established for any indication
58
SUMMARY (1 of 2)
• TSH is an adequate screening test for thyroid
function in a healthy older adult outpatient population,
but both free T4 and TSH should be used to evaluate
thyroid status in sick older adults
• Chronic adrenal insufficiency presents with
nonspecific symptoms such as anorexia, nausea,
weight loss, abdominal pain, weakness, hypotension,
and impaired function. It should be considered as a
cause of unexplained cachexia, mobility disability,
and hypotension, even in the absence of
hyponatremia and hyperkalemia.
59
SUMMARY (2 of 2)
• Vitamin D deficiency is common and not only
contributes to bone loss due to osteoporosis and
osteomalacia but also has been associated with
muscle weakness and falls.
• The most common causes of hypercalcemia are
primary hyperparathyroidism in outpatients, and
malignant hypercalcemia (eg, caused by squamous
cell cancers, breast cancer, myeloma, and
lymphoma) in the inpatient setting.
• There is little evidence of long-term clinical benefit
from supplementation with dehydroepiandrosterone
(DHEA), testosterone, and growth hormone in older
adults.
60
CASE 1 (1 of 4)
• A 69-year-old man is hospitalized with fatigue,
weakness, polyuria, anorexia, and confusion.
40-pack-year smoking history
Unintentional weight loss of 9 kg (20 lb) over the past 6
months
• Physical examination
Patient is lethargic and difficult to rouse.
Decreased breath sounds over right mid lung
Skin tenting
Dry mucous membranes
• Computed tomography: right hilar lung mass
61
CASE 1 (2 of 4)
• Laboratory findings






BUN
56 mg/dL
Creatinine
2.7 mg/dL
Albumin
2.6 g/dL
Calcium
13.2 mg/dL
Parathyroid hormone Low
Parathyroid hormone High related peptide (PTHrP)
• Management: aggressive IV hydration with normal saline,
followed by cautious administration of furosemide
• Patient’s mental status improves.
On following day, calcium level is 11.4 mg/dL and creatinine is 1.3 mg/dL.
62
CASE 1 (3 of 4)
Which one of the following should be initiated next?
A.
B.
C.
D.
E.
Alendronate
Zoledronic acid
Corticosteroids
Denosumab
Hemodialysis
63
CASE 1 (4 of 4)
Which one of the following should be initiated next?
A.
B.
C.
D.
E.
Alendronate
Zoledronic acid
Corticosteroids
Denosumab
Hemodialysis
64
CASE 2 (1 of 4)
• A 71-year-old man comes for follow-up related to
hypogonadism.
• History: osteoporosis, COPD, hypertension
Osteoporosis diagnosed after hip fracture 2 years ago. Lab
findings included serum testosterone level of 170 ng/dL.
He described erectile dysfunction, decreased libido, and fatigue.
• Current medications: alendronate, albuterol, ipratropium,
hydrochlorothiazide, IM testosterone cypionate (300 mg/2
weeks)
 He has adhered to therapy for the past 2 years, with good effect
and no adverse events.
65
CASE 2 (2 of 4)
• Examination
Patient is thin.
Bilateral gynecomastia
Slight decrease in size of testes
• Laboratory results
Serum total testosterone 600 ng/dL
Hematocrit
53%
Prostate-specific antigen 1 ng/mL
66
CASE 2 (3 of 4)
Which one of the following is the most appropriate
next step?
A.
B.
C.
D.
E.
Continue current regimen.
Reduce testosterone dosage.
Switch to testosterone gel or patch.
Measure prolactin level.
Start hydroxyurea.
67
CASE 2 (4 of 4)
Which one of the following is the most appropriate
next step?
A.
B.
C.
D.
E.
Continue current regimen.
Reduce testosterone dosage.
Switch to testosterone gel or patch.
Measure prolactin level.
Start hydroxyurea.
68
CASE 3 (1 of 4)
• A 71-year-old man is referred for follow-up after thyrotropin
level of 0.5 mIU/L was found during evaluation for memory
loss.
• He feels well and has no tremor, palpitations, or heat
intolerance.
• His wife is worried about his memory and his ability to drive.
• He has had trouble remembering plans they make with
friends.
• Recently, he got lost driving to a local restaurant that they
have been going to for years.
69
CASE 3 (2 of 4)
• Examination





Blood pressure 125/80 mmHg
Heart rate 72 bpm
BMI 23 kg/m2
Thyroid gland is of normal size, with no palpable nodules.
Normal ECG
• Laboratory findings:



Thyrotropin (repeat) 0.4 mIU/L
Free thyroxine 2 ng/dL
Total triiodothyronine 165 ng/dL
70
CASE 3 (3 of 4)
Which one of the following is the most appropriate next
step?
A.
B.
C.
D.
E.
Start treatment with propranolol.
Start treatment with propylthiouracil.
Refer for cognitive testing.
Order Holter monitoring.
Order echocardiography.
71
CASE 3 (4 of 4)
Which one of the following is the most appropriate next
step?
A.
B.
C.
D.
E.
Start treatment with propranolol.
Start treatment with propylthiouracil.
Refer for cognitive testing.
Order Holter monitoring.
Order echocardiography.
72
GRS9 Slides Editor:
Tia Kostas, MD
GRS9 Chapter Authors:
David A. Gruenewald, MD
Anne M. Kenny, MD
Alvin M. Matsumoto, MD
GRS9 Question Writer:
Lianne Hirano, MD
Managing Editor:
Andrea N. Sherman, MS
Copyright © 2016 American Geriatrics Society