Endocrine Issues in Older Adults

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Endocrine Issues in Older Adults

• Seki A. Balogun, MD

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Age-related changes in Endocrine Function

• Effects on Endocrine physiology from aging
• Occurs in a significant fraction of older adults
• No identifiable serious chronic illness
• Effects caused by age-related illness
• Occurs in a small proportion of elderly persons
• Sometimes difficult to differentiate

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Pituitary Gonadal Function

• Abrupt decline in ovarian function in women at
  about sixth decade (menopause)
• Decreased secretion of estrogens
• Increased FSH and LH
• Symptoms of menopause hot flashes
• Atrophic vaginitis
• Osteoporosis

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Pituitary Gonadal Function

• In men, gradual decline in testicular function
  (andropause)
• Varies from modest to severe (unclear clinical
  consequences)
• Sperm production stable from puberty to about age
  70
• Declines progressively to about 50 by age 90 yrs
• Tubular fibrosis and testicular shrinkage

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Hypothalamic- Pituitary Function

• Growth hormone
• Decreased secretion due to decreased GHRH
• Contributes to decrease in lean muscle mass and
  bone density
• Studies on rhGH replacement show reversal of
  effects
• Significant side effects DM and glucose
  intolerance, edema, carpel tunnel syndrome,
  arthralgias

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Vasopressin and Water balance

• Renal response to vasopressin reduced in older
  adults
• Decreased thirst in response to osmotic
  stimulation
• More vulnerable to water deprivation
• Hyponatremia common in the elderly
• SIADH hypersecretion of vasopressin with water
  retention
• Renal tubular dysfunction
• Decreased hydration
• Mineralocorticoid deficiency

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Melatonin

• Secretion lower in older adults, especially at
  night
• Probable cause of poor sleep
• Improvement in sleep with small doses of
  melatonin

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Adrenocortical function

• Cortisol and ACTH
• Variable age-related changes
• More variation during the day in older adults
• Related to sleep disorders
• Mean 24hr serum cortisol concentrations higher
• Associated with poor memory in women
• Lower bone density in men
• Increase in fractures in both men and women
• Minimal effect on response to acute illness

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Adrenocortical function

• Aldosterone
• Secretion decreases with age
• With mild renal insufficiency, can result in
  hypoaldosteronism (type IV RTA)
• Urinary sodium wasting
• Hyponatremia
• Hyperkalemia
• Dehydroepiandrosterone
• Decline with aging
• Clinical significance - unclear

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Thyroid function

• Thyroid hormones
• No changes in serum thyroxine (free and total)
• Mild decrease in clearance and production
• Decrease in dose requirements of thyroid hormone
  in hypothyroidism as patients age
• Mild decrease in T3 in the oldest old
• Less useful as an indicator of hypothyroidism in
  older adults
• Increased prevalence of high TSH in
  postmenopausal women (subclinical hypothyroidism)

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Parathyroid hormone

• PTH slightly higher in older adults
• Decreased serum calcium concentration
• Decreased intake and absorption
• Mild Vit D deficiency
• Decreased Vit D intake and absorption
• Decreased sun exposure
• Decreased conversion of 25-OHVit D to 1,25-OH2Vit
  D in the kidneys
• Relative resistance to 1,25-OH2Vit D action
• Phosphate retention by decreased renal function
• Contributes to osteoporosis, falls and fractures

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Insulin

• Hyperinsulinemia
• Decreased sensitivity to insulin in older adults
• Higher incidence of type 2 diabetes mellitus with
  increased age

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Common Endocrine Conditions in Older Adults

• Diabetes Mellitus
• Hypothyroidism

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Diabetes Mellitus

• 15 - 20 in persons 65 years and above
• Higher rates in persons over age 75 years
• Disease may be asymptomatic for many years
• One third of older adults with diabetes are not
  aware of diagnosis
• 10-year reduction in life expectancy
• Mortality rate twice that of persons without
  diabetes

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Classification

• Type 1 DM result of an absolute deficiency in
  insulin secretion due to autoimmune destruction
  of the beta cells of the pancreas
• Type 2 DM due to tissue resistance to insulin
  (relative insulin deficiency)

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Type 2 Diabetes Mellitus

• 90 of older adults with DM have the type 2 form
  of the disease
• Multifactorial etiology
• strong genetic predisposition
• life style changes (obesity, diet, decreased
  activity)
• age-associated decline in sensitivity to
  insulin

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Drug-induced hyperglycemia

• Medications can impair glucose tolerance
• Thiazide exacerbate insulin resistance
• Glucocorticoids antagonizes insulin action
• Atypical antipsychotics (clozapine, olanzapine)
  associated with weight gain, obesity,
  hypertriglyceridemia and DM
• Mechanism unclear

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Diagnosis

• Symptoms of polyuria, polydipsia and unexplained
  weight loss plus random plasma glucose of gt
  200mg/dl (11.1mmol/L)
• Fasting plasma glucose gt 126mg/dl (7.0mmol/L)
• 2hr postprandial plasma glucose level of
  gt200mg/dl (not usually performed)
• Should be confirmed on a subsequent day

American Diabetes Association (2001)
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Management

• Diet
• Specific dietary recommendation must be tailored
  for each individual
• Difficult to implement in the elderly as most are
  undernourished
• moderate caloric restriction 250-500cal less
  than usual intake , unless patient is
  significantly undernourished
• low fat diet (25-30 of total calories)
• Spaced small meals to avoid large caloric loads

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Management

• Physical activity
• Has to be individualized depending on functional
  status
• Surgeon Generals Report on Physical Activity and
  Health 1 hour of moderate physical activity on
  most days (3- 4 days a week)

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Drug Therapy

• Oral hypoglycemic agents
• Sulphonylureas
• Biguanides
• Thiazolidinediones
• Alpha- Glucosidase inhibitors
• Meglitinidines
• Insulin
• Beta-Cell Therapy

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Sulphonylureas

• Example Glipizide, Glyburide, Glimepiride
• Action
• Stimulate insulin secretion by islet cell
• Inhibit hepatic glucose production
• Side Effect hypoglycemia

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Biguanides

• Example Metformin
• Action
• Decrease hepatic glucose production
• Enhance insulin sensitivity in muscles
• Most effective in obese patients
• Side effect
• Gastrointestinal disturbance, weight loss,
  increase triglycerides, Lactic acidosis (renal
  insufficiency)

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Thiazolidinediones

• Examples Rosiglitazone (avandia)
• Action
• Increases insulin sensitivity in muscles
• Side effects
• Hepatic toxicity
• Edema

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Alpha- Glucosidase inhibitors

• Examples Acarbose (precose)
• Action
• Delays absorption of glucose by blocking alpha-
  glucosidase in the brush borders of the small
  intestine
• Side Effects
• Marked gastrointestinal disturbance (diarrhea,
  abdominal pain)
• Limited use

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Meglitinidines

• Examples Repaglinide (prandin)
• Action
• Stimulate insulin secretion by islet cells
• Inhibit hepatic glucose production
• Increase uptake of glucose by muscle
• Side Effect hypoglycemia

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Hypoglycemia

• Important side effect
• Difficult to detect in the elderly
• age-associated effects on autonomic system
• Age-associated changes in pharmacokinetics
• Longer duration of action
• Decreased metabolism
• Decreased excretion
• Caution with hypoglycemic agents

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Insulin

• Insulin therapy
• multiple-dose therapy feasible in highly
  motivated and functionally capable elderly
  patients
• Once a day or bid dosing used in most elderly
  patients
• Little experience with insulin pumps in the
  elderly used almost exclusively in type I DM

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Insulin therapy

• ADA recommendations for glucose control goals
• average preprandial plasma glucose
  90130mg/dl
• average bedtime glucose - 110-150mg/dl
• hemoglobin A1c 7- 8 (based on several studies)
• associated with significantly fewer microvascular
  complications

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Insulin therapy

• Rapid-acting
• Lispro (onset 15-30mins, peak1-3hrs,
  duration 3-6hrs
• Regular (onset 15mins-1hr, peak 2-6hrs,
  duration 4-12hrs)
• Semilente (onset 30mins-1hr, peak 3-10hrs,
  duration 8-18hrs)
• Intermediate-acting
• NPH (onset 1.5-4hrs, peak 6-16hrs,
  duration 14-28hrs)
• Lente (onset 1-4hrs, peak 6-16hrs,
  duration 14-28hrs)
• Long-acting
• Ultralente (onset 3-8hrs, peak 8-28,
  duration 24-40hrs)

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Insulin

• Complications of insulin therapy
• Hypoglycemia
• insulin allergy (most often with bovine insulin)
• antibody-mediated insulin resistance
• Lipodystrophy

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Complications- acute

• Hyperglycemic Hyperosmolar Nonketotic Coma
• usually in type 2 DM
• severe prolonged hyperglycemia
• severe dehydration
• intracellular hyperosmolarity
• altered mental status
• precipitating event/illness (meds, procedure,
  acute or chronic illness)
• Diabetic ketoacidosis
• usually in type 1 DM
• Precipitant infection, nonadherence to tx,
  severe dehydration
• Ketoacidosis
• AMS or coma

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Long Term Complications

• Surveillance for long term complications as soon
  as diagnosis is established
• As patients are often asymptomatic for many years
  before diagnosis
• Macrovascular (large blood vessel) disease
• Peripheral Vascular Disease of Extremities
• good foot care and examination
• special attention to early sensory changes loss
  of light touch , proprioception
• yearly podiatry follow-up

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Macrovascular complications

• Atherosclerosis and Coronary Artery Disease
• Screen and treat other cardiovascular risk
  factors aggressively
• Hyperlipidemia
• Smoking lifestyle change
• Acute Coronary Syndrome and Stroke prevention
  Aspirin
• Hypertension
• JNC VI recommendation
• treatment BP goal of lt130/85

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Microvascular Disease

• Retinopathy
• yearly ophthalmology visits
• Polyneuropathy
• peripheral neuropathy
• careful examination of feet
• autonomic neuropathy
• orthostatic hypotension, gastroparesis,
  impotence, neurogenic bladder

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Microvascular Disease

• Nephropathy
• microalbumin in urine
• albumin-to-creatinine ratio
• 24hr urine collection
• ACE-I slows progression of renal disease
• Caution in elderly with renal insufficiency risk
  of hyperkalemia

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Hypothyroidism

• Subclinical hypothyroidism
• Asymptomatic
• Elevation in serum TSH concentration
• Overt hypothyroidism
• Symptoms fatigue, cold intolerance,
  constipation, weight gain (not morbid obesity),
  bradycardia
• Coarse hair and skin, hoarseness, puffy facies
  (often attributed to aging)
• Hyperlipidemia
• Hyponatremia

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Hypothyroidism

• Primary thyroid disease in 95 of cases
• Screening test serum TSH
• Limitations
• Pituitary or hypothalamic dx
• Hospitalized, acutely/chronically ill patients
• Drugs which affect TSH secretion amiodarone,
  metoclopramide
• Treatment T4 replacement

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Subclinical Hypothyroidism

• General recommendations
• Treat if TSH gt 10mU/L
• May improve serum lipids
• Cardioprotective (linked with atherosclerosis and
  CAD)
• Improve non-specific symptoms

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Summary

• Several age-associated changes in endocrine
  function
• Menopause in women is the only well-defined,
  universal change with age
• Others changes are variable
• No well-defined age-adjusted normal levels for
  most hormones