Endocrine Function and Disorders

Question 1

Hormones

Answer 1

Some receptors are located on the surface of the cell.
Some receptors are located in the cell.

Question 2

Monitoring changes in hormone levels

Answer 2

Positive feedback: presence of the hormones stimulates increased production of the hormone until there is interruption of the cycle

Negative feedback: levels fall, stimulation, production, or secretion of the hormone increases
Vice versa, levels rise, stimulation, production or secretion of the hormone decreases

Question 3

Categories of endocrine disorders

Answer 3

Primary disorders - originate in the target gland responsible for producing the hormones

Secondary disorders - the target gland is essentially normal, but its function is altered by defective levels of stimulating hormones or releasing factors from the pituitary system

Question 4

Hormones essential for normal body growth and maturation

Answer 4

Growth hormone (GH)
Insulin
Thyroid hormone
Androgens

Question 5

Growth hormone

Answer 5

Necessary for linear bone growth in children

Question 6

Growth hormone in children

Answer 6

GH deficiency: interferes with linear bone growth. Results in short stature of Dwarfism.

GH excess: results in increased linear bone growth. Gigantism

Question 7

Acromegaly

Answer 7

Most common cause (95%) - somatotrope adenoma in anterior pituitary

When GH excess occurs in adulthood or after the epiphyses of the long bones have been fused, the condition is referred to as acromegaly.

Overgrowth of the cartilaginous parts of the skeleton. Enlargement of the heart and other organs of the body. Impaired glucose intolerance (hyperglycemia).

Question 8

Control of thyroid function

Answer 8

Follicles are functional unit of the thyroid.

Only T4 (93%) and T3 (7%) are released into the circulation.

Circulating T4 is converted to T3 when needed.

Stimulation by TSH from the pituitary gland.

Thyroid hormones are bond to thyroxine-binding globulin (TBG) and other plasma proteins for transport in the blood - only the free T3 and T4 can enter target cells and exert hormonal effects; protein bound forms cannot enter cells.

Protein bound thyroid hormones form a large reservoir that is slowly drawn on as free thyroid hormone as needed.

Question 9

Major functions of the thyroid hormone

Answer 9

Two major functions:
increases metabolism and protein synthesis.
necessary for growth and development in children (including mental development and attainment of sexual maturity)

These actions are mainly mediated by T3

Question 10

Alterations of thyroid function

Answer 10

Goiter: enlarged thyroid
Can occur with hyperthyroidism, euthyroid, and hypothyroidism
- not specific to disease entity or process but rather a term used as descriptor for enlarged thyroid gland

Question 11

Hypothyroidism Pathophysiology

Answer 11

Acquired hypothyroidism - destruction or dysfunction thyroid gland (primary hypothyroidism)
- thyroidectomy or gland ablation (iatrogenic)
- medications
- Hashimoto’s thyroiditis; autoimmune disorder, most common cause of acquired thyroidism
- thyroiditis; postpartum

Question 12

Congenital hypothyroidism

Answer 12

Thyroid hormone is essential for normal growth and brain development, almost half of which occurs during the first 6 months of life.

If untreated, congenital hypothyroidism causes mental retardation and impairs physical growth.

The manifestations of untreated congenital hypothyroidism are referred to as cretinism.

Question 13

Manifestations of hypothyroidism

Answer 13

Myxedema (nonpitting mucus type edema)

Constipation

Cold intolerance

Weight gain

Question 14

Hypothyroidism diagnostic data

Answer 14

Elevated TSH - best initial diagnostic test
Low Free T4

Question 15

Hypothyroidism treatment

Answer 15

Levothyroxine (T4) is drug of choice.
Taken 30 minutes before a meal - dietary interferes with absorption.
Not taken with other medications.

Lifelong thyroid hormone replacement therapy.

In the elderly “go low and go slow” approach.
Risk of inducing acute coronary syndrome.

Question 16

Hyperthyroidism pathophysiology

Answer 16

Condition of excess thyroid hormone
Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones

Graves disease: most common form in US
Autoimmune disorder of unknown etiology
Abnormal stimulation of the thyroid gland by thyroid-stimulate antibodies (TSH receptor antibodies) that act through normal TSH receptors

Question 17

Manifestations of hyperthyroidism

Answer 17

Wakefulness

Tachycardia

Diarrhea

Heat intolerance

Weight loss

Question 18

Graves disease

Answer 18

State of hyperthyroidism, goiter, and ophthalmopathy (proptosis).

An autoimmune disorder characterized by abnormal stimulation of the thyroid gland by thyroid-stimulating antibodies (thyroid-stimulating immunoglobulins [TSI]) that act through the normal TSH receptors.

Question 19

Graves disease diagnostic criteria

Answer 19

Serum TSH (markedly low)
T4 levels (markedly elevated)
Thyroid stimulating antibodies

Question 20

The adrenal gland

Answer 20

Adrenal glands - lie retroperitoneally at the apex of the kidney.

Aldosterone is principal mineralcorticoid.
Cortisol (hydrocortisone) is the major glucocorticoid.
Androgens are the chief sex hormones.

ACTH secreted by anterior pituitary gland controls the secretion of glucocorticoids and the adrenal androgens.

Cortisol, aldosterone and adrenal androgens secreted in unbound state and bind to plasma proteins for transport in the circulatory system.

Question 21

Steroid hormones produced by the adrenal cortex

Answer 21

Mineralcorticoids (aldosterone) -
regulating sodium, potassium, and water balance.

Glucocorticoids (cortisol) -
Aid in regulating the metabolic functions of the body: stimulate glucose production in liver; promotes protein breakdown; mobilizes fatty acids (cells utilize in lieu of glucose).
Controlling the inflammatory response
Essential for survival in stress situations

Adrenal sex hormones (androgens = DHEA) -
Little effect on normal sexual function
Pubertal growth body hair (pubic and axillary)

Question 22

Adrenal cortical insufficiency pathophysiology

Answer 22

Two forms of adrenal insufficiency

Primary insufficiency, or Addison disease caused by destruction of the adrenal gland -
Autoimmune destruction most common western societies (75%)
Tuberculosis in countries where prevalent
Bilateral adrenal hemorrhages; trauma, childbirth, open heart surgery or anticoagulants

Secondary adrenal insufficiency results from a disorder of the HPA system.

Adrenal gland cannot produce glucocorticoids, mineralcorticoids, or androgens.

ACTH levels increase to stimulate secretion of these hormones from the adrenal glands.

Question 23

Stages of adrenal cortical insufficiency

Answer 23

Primary adrenal cortical insufficiency (addison disease): ACTH levels are elevated because of lack of feedback inhibition

Question 24

Addison disease clinical manifestations

Answer 24

Darker pigmentation of skin (high ACTH).

Glucocorticoid deficiency - hypoglycemia, weakness

Mineralocorticoid deficiency - dehydration, hyponatremia, hyperkalemia

Question 25

Addison disease diagnostic criteria

Answer 25

Hyponatremia, hyperkalemia
High ACTH

Question 26

Cushing syndrome pathophysiology

Answer 26

Cushing syndrome refers to manifestations of hypercortisolism of any cause

Pituitary form - excess production ACTH by pituitary tumor (Cushing DISEASE).
Adrenal form - benign or malignant adrenal tumor.
Ectopic form - nonpituitary ACTH-secreting tumor (small cell carcinoma lung example).
Long-term administration of exogenous glucocorticoids (iatrogenic Cushing syndrome).

Question 27

Cushing syndrome clinical manifestations

Answer 27

Obesity of trunk, face, and upper back

Glucose intolerance

Suppression of inflammation/immunity

Protruding abdomen, sub clavicular fat pad = buffalo hump, round plethoric “moon” face

Question 28

Addison and Cushing syndromes

Answer 28

Addison disease is caused by destruction of the adrenal gland and glucocorticoid insufficiency.

In contrast, Cushing syndrome refers to the manifestations of hypercortisolism from any cause.

Question 29

Pancreas

Answer 29

Beta cells secrete insulin which regulates glucose utilization in tissues and reduces blood glucose levels.

Question 30

Diabetes Mellitus

Answer 30

Diabetes Mellitus is a group of metabolic disorders sharing the common feature of hyperglycemia.

Hyperglycemia in diabetes results from: defects in insulin secretion, defects in insulin action or most commonly, both

Question 31

Diabetes Mellitus pt 2

Answer 31

In the US, diabetes is the leading cause of end stage renal disease, adult-onset blindness and nontraumatic lower extremity amputations resulting from atherosclerosis of the arteries.

Disability epidemic -
sedentary lifestyle
poor eating habits
obesity

The most commonly identified signs and symptoms of diabetes are referred to as the three polys: polyuria (excessive urination), polydipsia (excessive thirst), and polyphagia (excessive hunger).

Question 32

Glucose homeostasis

Answer 32

The most important stimulus for insulin synthesis and release is glucose itself.

Question 33

Insulin action

Answer 33

Glucose uptake in other tissues besides striated muscle and adipocytes, most notably in the brain, is insulin independent.

Question 34

Criteria defining prediabetes*

Answer 34

FPG 100mg/dL to 125mg/dL (IFG) or A1C 5.7 to 6.4%

As many as one-fourth of individuals with impaired glucose intolerance will develop overt diabetes after 5 years.

Question 35

Criteria for diagnosis of diabetes

Answer 35

FPG ≥ 126mg/dL. Fasting is defined as no caloric intake for at least 8h.* or A1C ≥ 6.5% or In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL.

• in absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results on two separate days.

Question 36

Diabetes classification

Answer 36

Diabetes can be classified into the following general categories:

Type 1 Diabetes -
due to autoimmune beta-cell destruction, usually leading to absolute insulin deficiency.
5-10% of all cases.

Type 2 diabetes -
due to a progressive lost of adequate b-cell insulin secretion and frequently insulin resistance.
90-95% of all cases.

While the major types of diabetes have different pathogenic mechanisms, the long-term complications affecting the kidneys, eyes, nerves, and blood vessels are the same, as are the principal causes of morbidity and death.

Question 37

Acute complications of diabetes

Answer 37

Dawn Phenomenon: hormones (growth hormone, cortisol, and catecholamines) produced by the body cause the liver to release large amounts of glucose into the bloodstream. These hormones are released in the early morning hours. These hormones also may partially block the effect of insulin, whether it’s insulin your body produces or insulin from the last injection. if the body doesn’t produce enough insulin blood sugar levels may rise. This may cause high blood sugar in the morning before the person eats.

Somogyi Phenomena: can occur when a person is taking long-acting insulin for diabetes or develops hypoglycemia. Somogyi is caused by having too much insulin in the blood. If the blood sugar level drops too low, hormones (such as growth hormone, cortisol, and catecholamines) are released. These help reverse the low blood sugar level but may lead to blood levels that are higher than normal. A person’s body responds to the low blood sugar by causing a high blood sugar level. this can happen anytime but is an important consideration if blood sugars are high in the mornings.

Question 38

Hyperosmolar Hyperglycemic state

Answer 38

HHS is characterized by hyperglycemia, hyperosmolarity with dehydration, the absence of ketoacidosis, and depression of the sensorium. HHS occurs frequently in people with type 2 diabetes.

Hypoglycemia generally defines as any blood glucose concentration of less than 70 mg/dL, with or without symptoms.

Question 39

The chronic complications of diabetes

Answer 39

Disorders of microvasculature -
neuropathies
nephropathies
retinopathies

Disorders of gastrointestinal mobility (gastroparesis)

Macrovascular complications -
coronary artery
cerebral vascular
peripheral vascular disease

Foot ulcers

People with diabetes are also more susceptible to infections.

The level of chronic hyperglycemia is the best predictive factor for diabetic complications, glycemic control is a primary goal of diabetic treatment.