Endocrine Disorders

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Endocrinology

Overview

  1. Endocrinology is the study of chemical communication systems that provide the means to control a huge number of physiologic processes
  2. Two systems control all physiologic processes
    1. The nervous system sends electrical messages to control and coordinate the body
    2. The endocrine system uses chemicals to communicate, called hormones

Three general classes or groups of hormones (classified by chemical structure, not function)

  1. Steroid hormones (e.g., the sex hormones)
  2. Amino acid derivatives (e.g., epinephrine)
  3. Peptide hormones (e.g., insulin)

Endocrine System (the following are the major human endocrine glands)

Hypothalamus and Pituitary Gland

  1. Much of the endocrine system is controlled by hormones produced by cells in the hypothalamus
  2. A small but very crucial vascular system interconnects the hypothalamus and the anterior pituitary gland
  3. The hypothalamic hormones are secreted by specialized neurons called neurosecretory cells, located near the base of the pituitary stalk
  4. These hormones are carried by the blood vessels to the pituitary gland and stimulate it to secrete its hormones
  5. Pituitary gland is called the master gland because it controls many endocrine functions
  6. Most of the anterior pituitary hormones control the secretions of other endocrine glands (e.g., gonadotropic hormones to stimulate the gonads to release male or female hormones; also produces growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin)
  7. The hypothalamus also produces the hormones of the posterior pituitary gland and control their secretion (e.g., oxytocin for ejection of milk and uterine contractions at the time of childbirth; vasopressin [antidiuretic hormone] for regulation of urine output by the kidneys)

Thyroid Gland (and Parathyroid Gland)

  1. Thyroid hormones affect three fundamental physiologic processes (cellular differentiation, growth, and metabolism)
  2. Thyroid gland also produces calcitonin, and the parathyroid gland secretes the parathyroid hormone
    1. Both participate in control of calcium and phosphorus homeostasis and have significant effects on bone physiology

Pancreas

  1. Two functions
    1. It serves as a ducted gland, secreting digestive enzymes into the small intestines
    2. It also serves as a ductless gland by secreting insulin and glucagon to regulate the blood sugar level
      1. a. Glucagon tells the liver to take carbohydrates out of storage to raise a low blood sugar level that’s too low
      2. b. Insulin tells the liver to take excess glucose out of circulation to lower a blood sugar level that’s too high

Adrenal Glands

They sit on top of the kidney and consist of two parts

  1. Cortex, which secretes corticosteroids (e.g., cortisone)
    1. Well-known as being anti-inflammatory
    2. But they also suppress the immune system and can lead to susceptibility to infections
    3. Known to raise blood pressure
  2. Medulla, which secretes epinephrine (a.k.a., adrenaline) and other similar hormones
    1. Responds to stressors such as fright, anger, caffeine, or low blood sugar

Gonads

  1. The anterior pituitary gland secretes to the gonads, and the gonads secrete their own hormones (in addition to producing gametes)
  2. These hormones are called sex hormones
    1. Both sexes make some of each of the hormones, but testes secrete primarily androgens (e.g., testosterone), and ovaries make estrogen and progesterone

Pineal Gland

  1. Located near the center of the brain in humans and is stimulated by nerves from the eyes
  2. It secretes melatonin at night when it’s dark, thus secreting more in winter when the nights are longer
    1. Melatonin promotes sleep
    2. It affects reproductive functions by depressing the activity of the gonads
    3. It affects thyroid and adrenal cortex functions
    4. It is tied in to the circadian rhythm, annual cycles, and biological clock functions
    5. Linked to seasonal affective disorder – too much melatonin is produced

Common Endocrine Disorders

Diabetes Mellitus

Definition – DM is a disorder in which blood levels of glucose are abnormally high because the body doesn’t release or use insulin adequately

Types/Causes of DM

  1. Type I (IDDM)
    1. Pts. develop little or no insulin
    2. Of the 6% of the population with diabetes, only 10% have this type
    3. Diagnosis is before the age of 30
    4. Environmental factors (e.g., viral infection or nutritional factor in childhood or early adulthood) is thought to be the cause
    5. Some genetic predisposition is most likely needed for this to happen (e.g., short arm of chromosome 6)
  2. Type II (NIDDM)
    1. The pancreas continues to manufacture insulin, sometimes at even higher levels, but the body develops resistance to its effects, resulting in insulin deficiency
    2. Diagnosis is most typically after age 30, although children and adolescence can have it
    3. The prevalence becomes progressively more common with age
    4. 15% of people over 70 have Type II DM
    5. Obesity is a risk factor (80-90% of the obese have it)
    6. Blacks and Hispanics have a 2-3 times increased risk
    7. Tends to run in families
  3. Other causes
    1. High level of corticosteroids
    2. Pregnancy (i.e., gestational diabetes)
    3. Drugs
    4. Poisons that interfere with the production or effects of insulin
  4. Discuss Brittle Diabetes

Medical Symptoms

  1. Frequent urination – polyuria (kidneys are trying to dilute the glucose in urine)
  2. Excessive thirst – polydipsia
  3. Excessive hunger – polyphagia (loss of calories through urination causes weight loss, and the body needs to compensate for it).
  4. Other symptoms include blurred vision, drowsiness, nausea, and decreased endurance during exercise
  5. Those with poorly controlled DM have greater susceptibility to infections
  6. Weight loss almost always occurs before treatment in Type I, but most ppl with type II don’t lose weight
  7. In type I, sx begin abruptly and may progress rapidly to diabetic ketoacidosis (DKA)
    1. A condition in which fat cells begin to break down, producing ketones (toxic chemical compounds that can make the blood acidic)
    2. Initial sx include excessive thirst and urination, weight loss, nausea, vomiting, fatige, abdominal pain (esp. in kids), deep and rapid breathing, and coma if not treated
    3. DKA can occur even after starting insulin if they miss an injection or become stressed by an infection, accident, or serious medical condition
    4. Ppl with type II may not have sx for years or decades
      1. First sx of urination and thirst are mild at first and gradually worsen over weeks or months
      2. DKA is rare
      3. If blood sugar becomes very high, usually as a result of some superimposed stress (e.g., infection), the person may develop severe dehydration, which may lead to mental confusion, drowsiness, seizures, and a condition called nonketotic hyperglycemic-hyperosmolar coma

Complications

  1. Over time, elevated blood sugar levels damage blood vessels, nerves, and other internal structures
  2. Poorly controlled blood sugar also tend to cause the blood levels of fatty substances to rise, resulting in accelerated atherosclerosis
  3. Poor circulation through large and small blood vessels can harm the heart, brain, legs, eves, kidneys, nerves, and skin (making healing injuries slow)
  4. Long terms complications include things like MI, CVA, diabetic retinopathy, diabetic polyneuropathy, impotence in men, kidney failure, skin ulcers, gangrene of hands and feet, and amputations

Psychiatric Symptoms

Children and adolescents

  1. Kids are difficult to regulate medically
  2. Research has suggested that kids are quite resilient to psychopathology
  3. Longitudinal study by Kovacs et al. (1990)
    1. 14% of kids (out of 95) had premorbid dx
    2. 36% had dx within 3 mos. of onset – mostly adjustment disorder
    3. 93% of them had complete remission within 9 mos.
    4. As kids age, there may be a small increase in sx of depression, and in girls an increase in sx of anxiety
    5. Children who reported more difficulties in managing their diabetes also showed more symptoms of psychological distress
  4. Most cross-sectional studies have found no evidence of severe behavior or psychological problems in kids or adols.
  5. Some studies have suggested “tendencies toward anxiety and depression,” but not severe enough to meet diagnostic criteria

Adults

  1. Not as much research, but depression seems to be higher in adult DM compared to general population, but it is usually comparable to other chronic illnesses
  2. Type of diabetes does not appear to make a difference
  3. Certain concomitant medical factors appear to increase the risk of developing a psych disorder (e.g., macrovascular disease, retinopathy, peripheral neuropathy)

Neuropsychological Disorders

  1. Early onset in kids
    1. Early studies were able to show that IQ scores are significantly lower if diagnosed before the age of 5 – cause is thought to be organic
    2. Younger kids tested b/t 6 and 14, but dx by 4, show performance decrements (not just in IQ, but in other visuospatial measures)
    3. Girls more affected by boys
    4. By adolescence, impairments are across a broader range of domains
      1. IQ, attention, learning, memory, visuospatial ability, mental and motor speed
    5. 25% of adols. dx by age 5 met criteria for clinically significant impairment compared to only 6% of those dx after 5 and 6% of the nondiabetic comparison group
    6. Early onset kids and adols. have higher rate of severe hypoglycemia and have greater occurrence of seizures or LOC
    7. These kids also are more likely to show EEG abnormalities
  2. Later onset in kids
    1. These kids are much more comparable to their nondiabetic controls, with the exception of verbal IQ (more in girls) and academic achievement (more in boys)
      1. School absence was the greatest predictor of decline
      2. These kids may have undetected hypoglycemic events and miss stuff in class
  3. Cognitive function in adults with type I
    1. Evidence suggests that chronic hyperglycemia does have a negative impact on cognitive functioning once the type I-ers are in adulthood
    2. Deficits have been shown in complex novel problem solving ability, effortful learning, memory, attention, psychomotor speed, spatial information processing
    3. Theory is that chronic hyperglycemia may induce a “central neuropathy” that is characterized primarily by mental and motor slowing – deficits tend to be relatively small and unlikely to aversely affect ADLs
    4. Diabetic adults have slower brain stem auditory evoked potential latencies
    5. More likely to show abnormalities on MRI

End Stage Renal Disease (ESRD)

Definition

  1. Condition involving irreversible failure of excretory and regulatory functions of the kidneys
  2. Kidneys no longer sustain normal body functioning
  3. Requires renal replacement therapy for survival
  4. Associated cognitive deficits

Essential functions of the kidneys

  1. Controls the volume and composition of bodily fluids
  2. Excretes metabolites
  3. Produces or metabolizes hormones

Stages of renal failure

  1. Diminished renal reserve
    1. A measurable loss of renal function is noted
    2. Homeostasis is preserved at the expense of some hormonal adaptation (e.g., hyperparathyroidism)
  2. Renal insufficiency
    1. A slight retention of nitrogenous compounds (azotemia), which are reflected in elevated plasma urea and creatinine
  3. Uremia
    1. It’s the accumulation in the blood of constituents normally eliminated in the urine that produces a severe toxic condition
    2. Disturbed fluid and electrolyte balance
    3. Increased azotemia
    4. Systemic manifestations occur
      1. Pulmonary, cardiovascular, neurological, dermatological, gastrointestinal, hematological, and immunological systems

Most common causes of ESRD (top two are the most common in the US)

  1. DM
  2. HTN
  3. Chronic glomerulonephritis (one of the glomerulopathies)
  4. Chronic pyelonephritis
  5. Polycystic kidney disease

Early symptoms of ESRD

  1. Fatigue, drowsiness, apathy, lethargy, social withdrawal, personality changes, decreased concentration, diminished attention span

Progressed neuropsychological symptoms

  1. Confusion, inability to concentrate, decreased mental alertness, fatigability, intellectual impairment, impaired memory, sensory perception deficits, diminished perceptual-motor coordination

Common physical complaints

  1. Chronic fatigue, sexual dysfunction, headaches, nausea, leg cramps, sleep disturbances

If untreated, ESRD may result in delirium, coma, and eventually death

Anemia

  1. The cognitive deficits associated with chronic renal failure may not be explained solely by uremia, but also by the anemia that almost invariably accompanies it
  2. It’s detected in 90 percent of patients
  3. There are many contributing factors to this complication, but the most important cause is a decrease in erythropoietin production by the failing kidneys
  4. Severe anemia has been shown to be associated with cognitive dysfunction, reduced energy, and mood disturbances
  5. Recombinant human erythropoietin (rHuEPO) has provided effective treatment in reversing anemia in ESRD patients, thereby improving attention, mental processing speed, learning, memory, and mood

Treatment

  1. Hemodialysis
  2. Peritoneal dialysis (a.k.a., continuous ambulatory peritoneal dialysis)
  3. Kidney Transplantation

Neuropsychological Functioning

  1. Before treatment – reduced mental alertness, decreased concentration, fatigability, intellectual impairment, memory deficits, decreased psychomotor speed, and reduced perceptual-motor coordination
  2. After Treatment – dialysis improves cognitive functioning, but most studies report persistent deficits after the onset of dialysis, particularly in attention and concentration

Psychosocial Factors

  1. Depression
  2. Quality of life issues
  3. Interference with work, school, etc.
  4. Sexual dysfunction
  5. Marital and family discord
  6. Noncompliance with treatment

Hyperthyroidism

It is a condition in which the thyroid gland is overactive and produces too much hormone

  1. Many causes (some include:)
    1. Immunologic reactions (believed to be the cause of Graves’ disease)
    2. Thyroiditis – an inflammation of the thyroid gland that typically goes through a phase of hyperthyroidism
    3. Toxic thyroid nodules (adenomas) – areas of abnormal tissue growth within the thyroid gland
    4. Toxic multinodular goiter (Plummer’s disease) – a disorder in which there are many nodules
    5. Uncommon in adolescents and young adults and tends to increase with age
  2. Onset of hyperthyroidism can occur at any time during life span
    1. Peaks during the 3rd and 4th decades
    2. Occurs 7-10 more often in women (reason for sex difference is unknown)
    3. Regardless of the cause, the body’s functions speed up
  3. Symptoms include
    1. Heart palpitations, hypertension, person may feel warm even in a cool room, moist skin and diaphoresis, tremor, nervousness, fatigue and weakness, increased level of activity, increased appetite (but with weight loss), impaired sleep, frequent bowel movements, with occasionally with diarrhea
    2. Older adults may not show the above symptoms, but they may become weak, sleepy, confused, withdrawn, and depressed (sometimes called apathetic or masked hyperthyroidism)
      1. Heart problems, especially abnormal heart rhythms, are seen more often in older people
      2. Can cause changes in the eyes (puffiness, increased tear formation, irritation, unusual sensitivity to light, and the person appears to stare)
  4. Treatment is usually by medication, but other options include surgically removing the thyroid gland or treating it with radioactive iodine

Neurocognitive Effects

  1. Slower reaction time
  2. Impaired motor tasks, likely due to fatigue
  3. Mild deficits in attention, memory, and complex problem solving
  4. With proper treatment, most cognitive problems remit (although maybe not fully)
  5. Affective Features (improve or remit after euthyroidism is restored)
    1. Hyperthyroidism is believed to be accompanied by emotional instability/lability, general hyperactivity, irritability, easy fatigability, heat intolerance, feelings of apprehension, restlessness, and inability to concentrate

Hypothyroidism

A condition in which the thyroid gland is underactive and produces too little thyroid hormone. Very severe hypothyroidism is called myxedema

Causes

  • The most common cause is Hashimoto’s thyroiditis (an inflammation of the thyroid gland in which, for unknown reasons, the body turns against itself in an autoimmune reaction, creating antibodies that attack the thyroid gland)
    • The condition occurs eight times more often in women than in men and may occur in people with certain chromosomal abnormalities, including Turner’s, Down, and Klinefelter’s syndromes.
    • Many people with Hashimoto’s thyroiditis have other endocrine disorders such as diabetes, an underactive adrenal gland, or underactive parathyroid glands, and other autoimmune diseases such as pernicious anemia, rheumatoid arthritis, Sjögren’s syndrome, or systemic lupus erythematosus (lupus).
  • The second most common cause is treatment of hyperthyroidism
    • Both radioactive iodine treatment and surgery tend to produce hypothyroidism.
  • The common cause of hypothyroidism in many undeveloped countries is a chronic lack of iodine in the diet that produces an enlarged, underactive thyroid gland
    • Since salt manufacturers began adding iodine to table salt and iodine-containing disinfectants are often used to sterilize cow’s udders, this form of hypothyroidism has disappeared in the United States.
  • Even rarer causes of hypothyroidism include some inherited disorders in which an abnormality of the enzymes in thyroid cells prevents the gland from making or secreting enough thyroid hormones.
  • In other rare disorders, either the hypothalamus or the pituitary gland fails to secrete enough of the hormone needed to stimulate normal thyroid function.

Symptoms

  1. Insufficient thyroid hormone causes bodily functions to slow down.
  2. In sharp contrast to hyperthyroidism, the symptoms of hypothyroidism are subtle and gradual and may be mistaken for depression.
  3. Symptoms include dulled facial expressions, hoarse voice, slow speech, eyelids droop, puffy and swollen face and eyes, weight gain, constipation, inability to tolerate cold, hair that is sparse, coarse, and dry, and the skin that is coarse, dry, scaly, and thick.
  4. Many people develop carpal tunnel syndrome, which makes the hands tingle or hurt.
  5. If untreated, hypothyroidism can eventually cause anemia, a low body temperature, and heart failure.
    1. This may progress to confusion, stupor, or coma (myxedema coma)
  6. Treatment with thyroid hormone replacement therapy (oral medication) for life
  7. Neurocognitive effects
    1. Cognitive deterioration
    2. Onset and development of the cognitive impairments are usually subtle and insidious
    3. The patient becomes sluggish, lethargic, and suffers concentration and memory disturbances (and effects on motor speed)
    4. Some people, especially older people, may appear confused, forgetful, or demented–signs that can easily be mistaken for Alzheimer’s disease or other forms of dementia.
    5. Replacement therapy improves performance, but it may not completely reverse the effects
  8. Affective Features (reversed or greatly improved by thyroid replacement therapy)
    1. Hypothyroidism may be accompanied by symptoms of depression, emotional lability, mental sluggishness, indifference, self-accusatory ruminations, and suspiciousness
    2. Psychiatric presentation may be the first sign of hypothyroidism