Diseases and Disorders of the Endocrine System

Pancreatic Islet Disorders: Diabetes and Hyperinsulinism

Hyperinsulinism refers to an above-normal level of insulin in the blood of a person or animal.

Learning Objectives

Distinguish between the two types of hyperinsulinism: hyperglycemia and hypoglycemia

Key Takeaways

Key Points

  • Hyperinsulinism can be associated with several types of medical problems, which can be roughly divided into two broad categories: hyperglycemia and hypoglycemia.
  • Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than (200 mg/dl).
  • Hypoglycemia, or low blood sugar is an abnormally-diminished content of glucose in the blood. The principal problems arise from an inadequate supply of glucose to the brain, resulting in impairment of function (neuroglycopenia).

Key Terms

  • hyperinsulinism: Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal.
  • diabetes: A group of metabolic diseases whereby a person (or other animal) has high blood sugar due to an inability to produce, metabolize, or respond to the hormone insulin.
  • hypoglycemia: A too low level of blood glucose.

Hyperinsulinemia

This refers to an above-normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for one blood glucose level but low or high for another. Hyperinsulinism can be associated with several types of medical problems, which can be roughly divided into two broad and largely non-overlapping categories: those tending toward reduced sensitivity to insulin and high blood glucose levels (hyperglycemia), and those tending toward excessive insulin secretion and low glucose levels (hypoglycemia).

Hyperglycemia

Also known as hyperglycæmia, or “high blood sugar,” this is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than (200 mg/dl). Reference ranges for blood tests are 11.1 mmol/l, but symptoms may not start to become noticeable until even higher values such as 250–300 mg/dl or 15–20 mmol/l.

A subject with a consistent range above 126 mg/dl or 7 mmol/l is generally held to have hyperglycemia. Chronic levels exceeding 7 mmol/l (125 mg/dl) can produce organ damage.

Hypoglycemia

Hypoglycemia (not to be confused with hyperglycemia), or “low blood sugar,” is an abnormally-diminished content of glucose in the blood. The term literally means “low sugar blood.”

It can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose to the brain, resulting in impairment of function (neuroglycopenia). Effects can range from mild dysphoria to more serious issues such as seizures, unconsciousness, and (rarely) permanent brain damage or death.

The most common forms of hypoglycemia occur as a complication of treatment of diabetes mellitus with insulin or oral medications. Hypoglycemia is less common in non-diabetic persons, but can occur at any age. Among the causes are excessive insulin produced in the body (hyperinsulinemia), inborn error of metabolism, medications and poisons, alcohol, hormone deficiencies, prolonged starvation, alterations of metabolism associated with infection, and organ failure.

Hypoglycemia is treated by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods. In more severe circumstances it is treated by injection or infusion of glucagon.

Recurrent hypoglycemia may be prevented by reversing or removing the underlying cause, by increasing the frequency of meals, with medications like diazoxide, octreotide, or glucocorticoids, or by surgical removal of much of the pancreas.

The level of blood glucose low enough to define hypoglycemia may be different for different people, in different circumstances, and for different purposes, and occasionally has been a matter of controversy. Most healthy adults maintain fasting glucose levels above 4.0 mmol/L (72 mg/dl), and develop symptoms of hypoglycemia when the glucose falls below 4 mmol/L.

It can sometimes be difficult to determine whether a person’s symptoms are due to hypoglycemia. Criteria referred to as Whipple’s triad are used to determine a diagnosis of hypoglycemia.

Graph depicting glucose metabolism over the course of a day. The x-axis is time, with labels for each hour of the day (and indications of when breakfast, lunch, and dinner occurred). The y-axis is a measure of blood glucose in milligrams per deciliter. The trend lines show a spike in blood glucose and insulin immediately after each meal, with greater spikes for sucrose-rich food than for starch-rich food.

Glucose and Insulin Levels: Insulin rises in healthy adults as glucose intake increases.

Posttraumatic Stress Disorder (PTSD)

Posttraumatic stress disorder (PTSD) develops after exposure to an event that is so stressful for an individual that it becomes traumatic.

Learning Objectives

Describe the role of the endocrine system in post-traumatic stress disorder (PTSD)

Key Takeaways

Key Points

  • Three areas of the brain whose function may be altered in PTSD are the prefrontal cortex, the amygdala, and the hippocampus.
  • SSRIs (selective serotonin reuptake inhibitors) are considered to be a first-line drug treatment. SSRIs include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.
  • Cognitive behavioral therapy (CBT) seeks to change the way a trauma victim feels and acts by changing the patterns of thinking or behavior, or both, responsible for negative emotions.
  • PTSD symptoms may result when a traumatic event causes an over-reactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations.
  • Multiple studies show that parental PTSD and other posttraumatic disturbances in parental psychological functioning can, despite the best efforts of traumatized parents, interfere with their response to their child as well as their child’s response to trauma.

Key Terms

  • Posttraumatic stress disorder: Posttraumatic stress disorder (PTSD) develops after exposure to an event that is so stressful for an individual that it becomes traumatic.
  • cortisol: A steroid hormone (also called hydrocortisone), produced by the adrenal cortex, that regulates the metabolism of carbohydrates and maintains blood pressure.
  • SSRI: Selective serotonin re-uptake inhibitors are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders.

Posttraumatic stress disorder (PTSD) develops after exposure to an event that is so stressful for an individual that it becomes traumatic. Historically (DSM-IV) categorized as an anxiety disorder, it is now  categorized under “Trauma- and Stressor-Related Disorders” in the DSM 5.

The traumatic event may involve the threat of death to oneself or to someone else, or to one’s own or someone else’s physical, sexual, or psychological integrity, overwhelming the individual’s ability to cope. As an effect of psychological trauma, PTSD is less frequent and more enduring than the more commonly seen acute stress response. Diagnostic symptoms for PTSD include re-experiencing the original trauma through flashbacks or nightmares, avoidance of stimuli associated with the trauma, and increased arousal, such as difficulty falling or staying asleep, anger, and hypervigilance. Additionally, PTSD and other posttraumatic disturbances in parental psychological functioning can, despite the best efforts of traumatized parents, interfere with their response to their child as well as their child’s response to trauma.

PTSD is believed to be caused by experiencing any of a wide range of events which produces intense negative feelings of “fear, helplessness, or horror” in the observer or participant. Sources of such feelings may include (but are not limited to):

  • Experiencing or witnessing childhood or adult physical, emotional, or sexual abuse
  • Experiencing or witnessing physical assault, adult experiences of sexual assault, accidents, drug addiction, illnesses, and medical complications
  • Employment in occupations exposed to war (such as soldiers) or disaster (such as emergency service workers)
  • Getting a diagnosis of a life-threatening illness

Causes

Evolutionary psychology views different types of fears and reactions to fears as adaptations that may have been useful in the ancestral environment in order to avoid or cope with various threats. Mammals generally display several defensive behaviors roughly dependent on how close the threat is: avoidance, vigilant immobility, withdrawal, aggressive defense, appeasement, and finally complete, frozen immobility (the last possibly to confuse a predator’s attack reflex or to simulate a dead and contaminated body). PTSD may correspond to and be caused by overactivation of such fear circuits. Thus, PTSD avoidance behaviors may correspond to mammal avoidance of and withdrawal from threats.

PTSD symptoms may result when a traumatic event causes an over-reactive adrenaline response, which creates deep neurological patterns in the brain. PTSD causes biochemical changes in the brain and body that differ from other psychiatric disorders such as major depression. Most people with PTSD also show a low secretion of cortisol and high secretion of catecholamines in urine, with a norepinephrine to cortisol ratio consequently higher than comparable non-diagnosed individuals. These findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis.

Although most people (50–90%) encounter trauma over a lifetime, only about 8% develop full PTSD. Vulnerability to PTSD presumably stems from an interaction of biological diathesis, early childhood developmental experiences, and trauma severity. Predictor models have consistently found that childhood trauma, chronic adversity, and familial stressors increase risk for PTSD as well as biological markers of risk for PTSD after a traumatic event in adulthood. This effect of childhood trauma, which is not well-understood, may be a marker for both traumatic experiences and attachment problems.

Treatments

Modest benefits have been seen from early access to cognitive behavioral therapy, as well as from some medications such as propranolol. Critical incident stress management has been suggested as a means of preventing PTSD, but subsequent studies suggest the likelihood of its producing iatrogenic outcomes. A review of multiple studies, involving a number of different post-event psychological interventions structured to prevent PTSD .”..did not find any evidence to support the use of an intervention offered to everyone,” and that .”..multiple session interventions may result in a worse outcome than no intervention for some individuals.”

Cognitive behavioral therapy (CBT) seeks to change the way a trauma victim feels and acts by changing the patterns of thinking or behavior, or both, responsible for negative emotions. CBT have been proven to be an effective treatment for PTSD and is currently considered the standard of care for PTSD by the United States Department of Defense. In CBT, individuals learn to identify thoughts that make them feel afraid or upset and replace them with less distressing thoughts.

Eye movement desensitization and reprocessing (EMDR) is specifically targeted as a treatment for PTSD. Based on the evidence of controlled research, the American Psychiatric Association and the United States Department of Veterans Affairs and Department of Defense have placed EMDR in the highest category of effectiveness and research support in the treatment of trauma.

SSRIs (selective serotonin reuptake inhibitors) are considered to be a first-line drug treatment. SSRIs for which there are data to support use include: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Among the anti-depressants described in this section, bupropion and venlafaxine have the lowest patient drop-out rates. Sertraline, fluoxetine, and nefazodone have a modestly higher drop-out rate (~15%), and the heterocyclics and paroxetine have the highest rates (~20%+).

This is an image of the HPA Axis. Negative feedback affects the hypothalamus, which releases CRH into the anterior pituitary. Negative feedback can also affect the anterior pituitary directly, which releases ACTH into the adrenal cortex, which in turn releases CORT.

The hypothalmic-pituitary-adrenal axis.: The HPA axis is a major biological mechanism of stress and stress response

This image shows countries with high rates of posttraumatic stress disorder. The United States and Canada are among the countries with the highest incidence.

Post-traumatic stress disorder worldwide.: Incidences of PTSD by country (per 100,000 persons). The redder the country, the higher the incidence of PTSD.