Micro/Patho - Endocrine disorders

What is the most common cause of endocrine disorders?

Adenoma, or benign tumor, which is secretory, causing excess hormone, or destructive, causing hormone deficit

Other causes of endocrine disorders include...

- target cell resistance or insensitivity, e.g. type 2 diabetes mellitus
- congenital defects in the glands
- hyperplasia or infection
- abnormal immune reactions
- vascular problems

Put another way, normal activity of the endocrine system is disrupted by...

1) Impaired hormone synthesis or release
2) Abnormal interaction between hormone and target
3) Abnormal response of target to hormone

Endocrine disease consists of what two factors?

1) Under/over production of hormones
2) Development of mass or lesions

What are the characteristics of hyperpituitarism?

- usually due to adenoma of anterior lobe
- leads to excess secretion of a single hormone
- most common type is prolactinoma, which causes amenorrhea, reduced libido, infertility and galactorrhea (spontaneous flow of milk)

What is the second most common adenoma of the pituitary and what are its variants?

Growth hormone adenoma, causing excess GH secretion.
It's variants are acromegaly (adulthood) or gigantism (childhood or adolescence). The distinction depends on whether the epiphyses of the long bones have fused and adult height achieved.

What are the effects of acromegaly?

Affects small bones and cartilage - hands, feet, skull, jaw
S/S - HA, fatigue, enlarged hands/feet, joint pain, limited joint movement, protruding jaw, broad lower face

What are the effects of gigantism?

Affects all bones, muscles and organs
S/S - HA, frontal bossing, double vision, disproportionately long arms & legs

Excess GH may also be associated with what other conditions?

Diabetes mellitus
Hypertension
Arthritis
CHF

What are the causes of hypopituitarism?

- More than half by non-secreting pituitary adenoma
- Also caused by ischemic necrosis ablation by radiation or surgery
- Genetic or acquired abnormality
* Hypopituitarism occurs with >75% loss of anterior lobe

What three conditions are associated with hypopituitarism?

Sheehan syndrome
Diabetes insipidus
Syndrome of Inappropriate ADH secretion (SIADH)
* The latter two affect the posterior pituitary

What are the characteristics of Sheehan syndrome?

Caused by postpartum ischemic necrosis of anterior pituitary
S/S - fatigue, low blood pressure, lack menstruation, lose pubic and axillary hair, inability to breastfeed

What are the characteristics of diabetes insipidus?

deficiency of ADH results in - excessive water loss
S/S - hypernatremia, thirst (polydipsia), excess urination
Risk - dehydration

What are the characteristics of Syndrome of Inappropriate ADH secretion (SIADH)?

excess ADH results in excessive water reabsorption
S/S - hyponatremia, cerebral edema ? neurologic dysfunction (confusion, loss consciousness) fatigue, HA, convulsions, weakness

What five conditions are related to thyroid dysfunction?

- Hyperthyroidism, e.g. Grave's disease
Hypothyroidism (3):
- Hashimoto's thyroiditis
- Cretinism
- Myxedema
- Goiter (enlargement of the thyroid)

What are the characteristics of hyperthyroidism?

Increased secretions of T3 and T4 hormones, which induce a hypermetabolic state and overactive sympathetic response. Grave's disease is the most common form and represents a hypersensitivity type II disorder (autoantibodies stimulate TSH receptors of the

What are the signs and symptoms of Grave's disease?

increased appetite, sweating, nervous, restless, weight loss, fatigue, exophthalmos (bulging eyes)
skin - warm, flushed, heat intolerant
GI hypermobility, diarrhea, malabsorption, tachycardia, palpitations, tremor

What are the characteristics of cretinism?

- Develops in infancy or early childhood
- Inadequate skeletal and nervous development
- d/t lack of iodine or developmental defect
- thyroid gland non-functional or absent
- severe impairment of all aspects of growth and development

What are the signs and symptoms of cretinism?

severe mental retardation, short stature, dull look, puffy face, protruding tongue, lack muscle tone, sleepy, poor feeding, poor growth, dry hair

What are the characteristics of myxedema?

- Develops in adults
- Inadequate thyroid hormone
- refers to unique form of edema

What are the signs and symptoms of myxedema?

generalized apathy, mental sluggish, lethargy, cold intolerant, dry skin, hair loss, weakness, constipation, slow reflexes, weight gain, puffy hands and feet

What are the characteristics of Hashimoto disease?

- Most common cause of hypothyroidism in USA
- Autoimmune disease that has primary T cell defect
- Cytotoxic CD8 cells destroy thyroid epithelia, induce thyroiditis
- Subsequently B cells produce Ab against TSH receptors
- Presents as painless enlargement

What is the key takeaway of Hashimoto's disease?

Autoimmune disease destroys the thyroid's sensitivity to TSH and subsequently reduces thyroid hormone production.

What are the characteristics of goiter?

Visible enlargement of the thyroid endemic to mountainous regions usually d/t lack of iodine. Can be the result of hypo- or hyperthyroid conditions. Results from excessive or compensatory production of TSH leading to hyperplasia and hypertrophy in the thy

What are the signs and symptoms of goiter?

large neck mass, airway obstruction, dysphagia, compression of vessels in neck

What conditions affect the parathyroid glands?

Hyper- and hypoparathyroidism

How do hyper- and hypoparathyroidism affect serum calcium levels?

Because PTH causes bone to release calcium, hyperparathyroidism causes hypercalcemia, and hypoparathyroidism causes hypocalcemia.

What are the characteristics of the primary type hyperparathyroidism?

- most common problem with parathyroids
- overproduction of PTH leads to hypercalcemia
- caused by adenoma or hyperplasia
- Classic manifestation "painful bones, renal stones, abdominal groans, psychic moans

What are the signs and symptoms of the primary type of hyperparathyroidism?

constipation, nausea, gallstones, kidney stones, polyuria, back pain, joint pain, blurred vision, loss appetite, itchy, fatigue, fractures of long bones, decreased height

What are the characteristics of the secondary type of hyperparathyroidism?

- Due to chronic low levels of Ca++ activates parathyroids
- Renal failure
- S/S - metastatic calcification of lungs, vessels, heart, stomach

Which hormones are produced by the different areas of the adrenal glands?

Cortex produces cortisol and aldosterone
Medulla produces epinephrine and norepinephrine

What three diseases are associated with adrenal dysfunction?

1) Cushing's disease - hypercortisolism
2) Hyperaldosteronism
3) Addison's Disease - chronic adrenal insufficiency

What are the characteristics of Cushing's disease?

Excess glucocorticoid d/t exogenous exposure (drug treatment) or endogenous hypersecretion of ACTH. Can cause suppressed glucose metabolism, leading to hyperglycemia, polydipsia and diabetes mellitus.

What are the symptoms of Cushing's disease?

moon facies, redistribution of lipids, upper body obesity, buffalo hump, bruise easily, striae on abdomen, menses irregular/stop, hirsutism, mood swings, acne

What are the characteristics of Hyperaldosteronism?

Adrenal adenoma or adrenal hyperplasia causes excess secretion of aldosterone, resulting in sodium retention and potassium secretion (hypokalemia).

What are the signs and symptoms of Hyperaldosteronism?

Hypertension and hypokalemia, leading to dysrhythmia, reduced GI motility, reduced renal function, prickly/tingly sensation, and neuromuscular malfunction.

What are the characteristics of Addison's Disease?

Destruction of the adrenal cortex by autoimmune reaction, viral infection (TB, AIDS), or tumor leads to adrenal hormone insufficiency. The condition has a slow onset.

What are the signs and symptoms of Addison's Disease?

early: progressive weakness and easy fatigue
- GI disturbance: diarrhea, N/V, loss appetite, weight loss
- hyperpigmentation of skin, mouth lesions
- sodium loss and potassium retention (salt craving)
- hyperkalemia, hyponatremia, hypovolemia, hypotension

What symptoms do Addison's disease and Cushing's disease have in common?

High risk of infection and poor stress response

What are the characteristics of hypogonadism?

Sex glands produce little or no hormones, typically caused by genetic disorders. Also caused by nutritional deficiency, radiation, surgery, medication, trauma

What are the signs and symptoms of hypogonadism?

During childhood - no sexual maturation
During adulthood - low sex drive, hot flashes, loss body hair, impotence
* Adult hypogonadism can be physiologic

What are the general characteristics of diabetes mellitus (types I and II)?

A relative or absolute deficiency in insulin (insulin resistance or deficient production) results in abnormal carbohydrate, fat and protein metabolism. ~ 13 million cases USA, 35,000 deaths annually.

What are the characteristics of Type I diabetes mellitus?

- Formerly juvenile or insulin-dependent
- Accounts for 5 - 10% of cases
- IA - autoimmune destruction of ? cells
- IB - severe insulin deficiency without autoimmune disease
- Characterized by absolute deficiency of insulin production, destruction of ? ce

What are the mechanisms of ? cell destruction in Type I diabetes mellitus?

- Genetic susceptibility - MHC alleles predispose patients
- Autoimmunity attacks ? cells
- Environmental insult - renders ? cells immunogenic
Morbillivirus - measles
Paramyxovirus - mumps
Togavirus - rubella
Epstein-Barr virus - infectious mononucleosis

What are the clinical features of Type I diabetes mellitus?

Polyuria - profound loss of water and electrolytes
Polydipsia - intense thirst
Polyphagia
Weight loss
Ketoacidosis - due to breakdown of lipids to make energy

What's a good way to understand the mechanism of Type I diabetes mellitus?

d/t the destruction of ? cells, the pancreas cannot produce insulin. This leads to hyperglycemia and inadequate glucose availability to several tissue types. Hyperglycemia leads to osmotic imbalance, fluid loss, electrolyte imbalance and intense thirst. U

What are the characteristics of Type II diabetes mellitus?

- Formerly non-insulin dependent or adult
- Accounts for ~ 80% of cases
- Epidemic increase among obese
- Characterized by impaired insulin production, insulin resistance, or both

Describe the development of Type II diabetes mellitus

Genetic defects can lead to impaired insulin production. Alternatively, obesity can result in insulin resistance. Either or both of these can lead to hyperglycemia and ? cell exhaustion = type II diabetes mellitus.

DM has the complication of non-enzymatic glycosylation. What is this process and why is it problematic?

Excess glucose binds to free amino acids or proteins, e.g. collagen and hemoglobin. These can lead to thickening of the basement membrane of vessel walls and attract cholesterol. Atherosclerosis is a frequent complication of DM.

DM has the complication of intracellular hypergylcemia. What is this process and why is it problematic?

Tissues that do not depend on insulin (nerves, kidneys, lens, blood vessels) absorb excessive glucose from the blood. This is converted to sorbitol and fructose, increasing the cells osmolarity, leading to hydropic swelling and cell injury.

What are the five most common complications of DM?

Types I and II lead to:
1) Accelerated atherosclerosis - MI (most common killer, hardening of arteries, build up of plaque)
2) Nephropathy - kidney damage (2nd most common killer)
3) Neuropathy - nerve damage: tingling, pain, numbness
4) Retinopathy - dam

Review?

sure

The pituitary is affected by which disorders? What are their respective hormone imbalances?

Prolactinoma - excessive prolactin
Acromegaly - excessive GH in adults
Gigantism - excessive GH in children, adolescents
Sheehan syndrome - panhypopituitarism (all hormones inadequate)
Diabetes insipidus - deficient ADH
Syndrome of inappropriate ADH secre

The thyroid is affected by which disorders? What are their respective hormone imbalances?

Hyperthyroidism (Grave's disease) - excess T3 and T4
Cretinism - thyroid gland non-functional or absent
Myxedema - Inadequate thyroid hormone
Hashimoto disease - Inadequate thyroid hormone
Goiter - excessive or inadequate thyroid hormone causes excess TSH

The parathyroids are affected by which disorders? What are their respective hormone imbalances?

Primary and secondary parathyroidism - excess PTH
Hypothyroidism - inadequate PTH

The adrenal glands are affected by which disorders? What are their respective hormone imbalances?

Cushing's disease - excess glucocorticoid or ACHT
Hyperaldosteronism - excess aldosterone
Addison's disease - inadequate adrenal hormones

The gonads and pancreas are affected by which disorders? What are their respective hormone imbalances?

Hypogonadism - inadequate sex hormone
Diabetes mellitus - relative or absolute insulin insufficiency