Endocrine MT1

T/F: Osteoporosis is a well-recognized complication of cushing's syndrome.

True

What does cortisol inhibit and create in individuals with osteoporosis?

Inhibit leydig cell function resulting in hypogonadism

What do leydig cells make?

Sperm

What is decreased when leydig cell function is inhibited?

Fertility chances

What is the term used for "bug eyes"?

Exophthalmos

What is exophthalmos?

Retro-orbital pads that are filled with fat and push the eyeball forward

What is an example of a clinical sequelae for osteoporosis?

Hypertension

What are the additional sequelae for osteoporosis?

Hypogonadism and exophthalmos

T/F: Hypertension is seen in 74% of individuals effected by osteoporosis.

True

What is increased when the R2A system is turned on?

Endothelin secretion

What does hypercortisolism sensitize?

Norepinephrine receptors on the tunica media of arterioles

What does hypercortisolism defeat?

11b-HSD2

What happens after hypercortisolism defeats 11b-HSD2?

Cortisol binds with overstimulated aldosterone mineralocorticoid receptors

What do mineralocorticoid receptors stimulate?

Reabsorption of salt and water, excretion of potassium and hydrogen ions

What is the mechanism of hypertension?

Arterioles are over vasoconstricted

What do excess levels of cortisol cause?

Increased bony resorption, increased urinary excretion of calcium, decreased bony formation, decreased calcium absorption in intestine

What is a result of osteoporosis?

Bones have less calcium content and are susceptible to fracture

What is common in cushing's disease?

Weight gain and obesity that increase stomach to waist/thigh ratio (centripetal weight gain)

Where do fat deposits occur in relation to cushing's disease?

Epidural space

What do fat deposits in the epidural space lead to?

Central or lateral stenosis, radicular pain, and radiculopathy

T/F: About 50% of patients with ACTH dependent cushing's disease also have skin pigmentation.

False; 15%

What do increased levels of ACTH cause?

Melanocyte binding in the skin

What does melanocyte binding in the skin cause?

Over secretion/injection of melanin into keratinocytes

How do keratinocytes react to melanin injection?

They become more brown/black and oral cavity is affected

What two conditions can cause hyperpigmentation?

Addison's disease and ACTH dependent cushing's syndrome

What happens in ACTH dependent cushing's syndrome?

ACTH levels pile up and cause adrenal gland dysfunction with no cortisol secretion

T/F: If there are too many melanocytes the skin will become darkened.

True

What can excessive insulin cause?

Prolong the life of keratinocytes making them pile up

What is acanthosis nigricans characterized by?

Velvety hyperpigmentation of the skin

Where is velvety hyperpigmentation of the skin found?

In intertriginous areas such as the nape of the neck and extensor surfaces

What conditions involve skin discolorations that cause insulin resistance?

Diabetes mellitus and cushing's syndrome

Where does excess insulin bind to?

IGF-1R receptors

Where are IGF-1R receptors located?

On basal cells in the stratum basale

What occurs after insulin binds to IGF-1R receptors

Overproduction of melanocytes, keratinocytes, and fibroblasts

What conditions is acanthosis nigricans typically seen in?

Insulin resistance conditions and hyperglycemia

T/F: Acanthosis nigricans is occasionally seen in internal maligancy.

True

What is the number one internal malignancy?

Gastric adenocarcinoma

What are clinical sequelae the result of?

Chronic exposure to excessive serum glucocorticoid (cortisol) levels

T/F: Cushing's syndrome is very easy to diagnose because it presents with familiar symptoms.

False; presents with many different symptoms which makes it hard to diagnose

What are the clinical manifestations of cushing's syndrome?

Obesity, rounding of face, brusining, thin skin, buffalo hump, stretch marks, hirsutism, muscle weakness, hypertension, diabetes, osteoporosis, acanthosis nigricans

T/F: Truncal obesity is seen in about 90% of adults with limb atrophy.

True

What does excessive production of glucocorticoids stimulate?

Lipoprotein lipase and hormone sensitive lipase

What does central fat uptake create?

Truncal obesity, moon face, buffalo hump

What does hormone sensitive lipase cause?

Fat and protein breakdown in the periphery

What does hypercortisolism create?

Blood vessel weakness leading to spontaneous bruising

What does excess cortisol interfere with?

Binding of insulin to skeletal muscle and fat cell receptors

What is the job of cortisol?

Keep blood sugar high

What happens if there are no GLUT-4 transporters?

No glucose uptake in cell

What is the result of no glucose uptake in skeletal muscle and fat cells?

Hyperglycemia

T/F: GLUT1, GLUT2, GLUT3, and GLUT5 are all insulin independent.

True

What areas is GLUT1 found in?

Blood, blood-brain barrier, heart

What areas is GLUT2 found in?

Liver, pancreas, small intestine

What areas is GLUT3 found in?

Brain, neurons, sperm

What areas is GLUT4 found in?

Skeletal muscle, adipose tissue, heart

What areas is GLUT5 found in?

Enterocyte of intestinal epithelium

T/F: The only insulin dependent GLUT protein is GLUT4.

True

What are the two causes of cortisol overproduction?

Iatrogenic use of glucocorticoids and adrenal gland adenoma

What is adrenocortical adenoma made of?

Mutated fasciculata that over secrete cortisol

T/F: The incidence of adrenocortical adenoma is 7% in patients over 70 years of age.

True

T/F: Adrenocortical adenoma is classified as a malignant neoplasm.

False; benign neoplasm

T/F: Adrenocortical adenoma can be functional and secrete hormones such as cortisol, aldosterone, DHEA, andostenedione, and testosterone.

True

What is the prognosis of adrenocortical adenoma?

38% of people have a 5 year survival rate with chemotherapy

T/F: The cortisol-secreting mutated fasciculata cells can metastasize into the bloodstream easily.

True

What is primary pigmented nodular adrenocortical disease (PPNAD) known as?

Primary pigmented nodular adrenal hyperplasia

T/F: PPNAD occurs in childhood and represents 2% of ACTH independent cushing's disease individuals.

True

What must people with chronic inflammatory diseases take?

Exogenous glucocorticoids

What do exogenous glucocorticoids do?

Prevent inflammatory damage of joints and organs

T/F: Individuals taking exogenous glucocorticoids have 5 times higher the normal secreted levels of cortisol.

False; 3 times

What do exogenous glucocorticoids shut off?

HPA axis through double negative feedback

What cannot restart if a patient tries to come off of glucocorticoids?

HPA axis

T/F: A five-year survival rate for untreated cushing's disease is approximately 50%.

True

What are the two causes of cushing's disease?

ACTH dependent causes and ACTH independent causes

What is the number one cause of cushing's syndrome?

ACTH dependent cushing's disease

What is cushing's disease caused by?

Anterior pituitary tumor

What is the anterior pituitary tumor created by?

ACTH-secreting corticotroph adenoma

What is the anterior pituitary tumor of cushing's made of?

Mutated, yet functional corticotrope cells

Where does ACTH travel to and what does it stimulate?

Adrenal cortex and over stimulates fasciculata cells

T/F: Pituitary adenomas are made of mutated corticotroph cells which do not have receptors to bind cortisol.

True

T/F: ACTH overproduction in cushing's patients can be shut off.

False; no way to shut off the overproduction

T/F: 25% of patients with cushing's disease develop bilateral adrenocortical hyperplasia as a sequelae.

True

What does overuse and overstimulation cause the adrenal gland to become?

Enlarged

What two conditions enlarge the adrenal gland?

Bilateral adrenocortical hyperplasia and bilateral macronodular adrenal hperplasia

T/F: 15% of cushing's patients have extra-HPA axis tumors that ectopically secrete ACTH.

True

Where are HPA axis tumors that ectopically secrete ACTH found?

Lungs

T/F: HPA axis tumors that ectopically secrete ACTH are not cancerous.

False; they are cancerous

What type of HPA axis cancer cells are found in the lungs?

Small cell carcinoma, bronchial carcinoid cancer

Where are adenoma of parvocellular neurons located?

Paraventricular nuclei

What do mutated cells of adenoma parvocellular neurons secrete?

Corticotropin releasing hormone (CRH)

T/F: CRH is a hormone which can find its way back to the anterior

pituitary to overproduce ACTH.

True

What else does ACTH bind to?

Zona reticularis

What happens when ACTH binds to the zona reticularis?

Overproduction of adrenal androgens

What is cushing's syndrome also known as?

Hypercortisolism

What do decreased levels of cortisol stimulate?

Release of corticotopin releasing hormone (CRH)

What does CRH stimulate?

Release of cortisol form adrenal gland

What is CRH released by?

Parvocellular neurons in the paraventricular space of hyppthalamus

Where is CRH dumped?

Hypophyseal portal system

Where do the hypophyseal portal vessels carry CRH?

Anterior pituitary gland

What will high levels of cortisol kick off?

Double negative feedback loop

What does the double negative feedback loop turn off?

CRH production and ACTH production

What does CRH production inhibit?

Parvocellular neurons