Endocrine Function and Disorders Flashcards
Hormones
Some receptors are located on the surface of the cell.
Some receptors are located in the cell.
Monitoring changes in hormone levels
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
Categories of endocrine disorders
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
Hormones essential for normal body growth and maturation
Growth hormone (GH)
Insulin
Thyroid hormone
Androgens
Growth hormone
Necessary for linear bone growth in children
Growth hormone in children
GH deficiency: interferes with linear bone growth. Results in short stature of Dwarfism.
GH excess: results in increased linear bone growth. Gigantism
Acromegaly
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).
Control of thyroid function
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.
Major functions of the thyroid hormone
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
Alterations of thyroid function
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
Hypothyroidism Pathophysiology
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
Congenital hypothyroidism
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.
Manifestations of hypothyroidism
Myxedema (nonpitting mucus type edema)
Constipation
Cold intolerance
Weight gain
Hypothyroidism diagnostic data
Elevated TSH - best initial diagnostic test
Low Free T4
Hypothyroidism treatment
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.
Hyperthyroidism pathophysiology
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
Manifestations of hyperthyroidism
Wakefulness
Tachycardia
Diarrhea
Heat intolerance
Weight loss
Graves disease
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.
Graves disease diagnostic criteria
Serum TSH (markedly low)
T4 levels (markedly elevated)
Thyroid stimulating antibodies
The adrenal gland
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.
Steroid hormones produced by the adrenal cortex
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)
Adrenal cortical insufficiency pathophysiology
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.
Stages of adrenal cortical insufficiency
Primary adrenal cortical insufficiency (addison disease): ACTH levels are elevated because of lack of feedback inhibition
Addison disease clinical manifestations
Darker pigmentation of skin (high ACTH).
Glucocorticoid deficiency - hypoglycemia, weakness
Mineralocorticoid deficiency - dehydration, hyponatremia, hyperkalemia
Addison disease diagnostic criteria
Hyponatremia, hyperkalemia
High ACTH
Cushing syndrome pathophysiology
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).
Cushing syndrome clinical manifestations
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
Addison and Cushing syndromes
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.
Pancreas
Beta cells secrete insulin which regulates glucose utilization in tissues and reduces blood glucose levels.
Diabetes Mellitus
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
Diabetes Mellitus pt 2
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).
Glucose homeostasis
The most important stimulus for insulin synthesis and release is glucose itself.
Insulin action
Glucose uptake in other tissues besides striated muscle and adipocytes, most notably in the brain, is insulin independent.
Criteria defining prediabetes*
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.
Criteria for diagnosis of diabetes
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.
Diabetes classification
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.
Acute complications of diabetes
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.
Hyperosmolar Hyperglycemic state
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.
The chronic complications of diabetes
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.
