Endo Exam 1: Sharma Endo/Adrenal

______ are potent chemical substances secreted by specialized organs that circulate in blood and act on specific target cells distant from their source of secretion.

Hormones

______ glands release their secretions into a duct (e.g., salivary, sweat, lacrimal, mammary glands).

Exocrine

______ glands release their secretions directly into the blood.

Endocrine

The ______ and ______ are mixed glands with both exocrine and endocrine functions

Pancreas, Liver

The thyroid gland secretes ______, ______, and ______.

T3, T4, calcitonin

The adrenal glands secrete ______ and ______.

The ovaries secrete ______ and ______.

The testes secrete ______.

Cortisol, mineralocorticoids, Progesterone, estrogen, Testosterone

The ______ serves as an interface between neuronal inputs and the endocrine system, and regulates the master gland, the ______.

Hypothalamus, pituitary gland

The pituitary gland regulates the ______, ______, ______, and ______.

Gonads, thyroid, mammary gland, adrenals

The hypothalamic releasing hormone for the gonads is ______.

Gonadotropin-releasing hormone (GnRH)

The three pituitary hormones mentioned are ______, ______, and ______.

LH, TSH, ACTH

The three categories of hormones based on chemical structure are ______, ______, and ______.

Steroid, peptide/protein, AA derivative hormones

Steroid hormones from the gonads include ______, ______, and ______.

Estradiol, progesterone, testosterone

Steroid hormones from the adrenal gland include ______ and ______.

Cortisol, aldosterone

Name the 5 peptide/protein hormones from the pituitary: ______, ______, ______, ______, ______.

GH, FSH, LH, TSH, ACTH (also prolactin)

The pancreas secretes the peptide hormones ______ and ______.

Insulin, glucagon

______ is a peptide hormone from the thyroid, and ______ is a peptide hormone from the parathyroid

Calcitonin, PTH

The amino acid derivative hormone from the thyroid is ______.

______ is an AA derivative hormone from the adrenal gland, derived from ______

______ is an AA derivative hormone from the pineal gland, derived from ______

Thyroxine, EPI, tyrosine, Melatonin, tryptophan

Peptide/protein hormones are ______ (hydrophilic/hydrophobic), while steroid hormones and thyroxine are ______ (hydrophilic/hydrophobic).

Hydrophilic, hydrophobic

Hydrophobic hormones act via ______ receptors, while hydrophilic hormones act via ______ receptors.

Nuclear, cell surface

Hydrophobic hormones circulate in blood bound to ______, such as SBP, SHBG, and TBG

Plasma proteins (steroid-binding proteins, sex hormone-binding globulin, thyroxine-binding globulin)

Only ______ hormone is available for binding to receptors and undergoing metabolic inactivation.

Plasma protein binding results in a ______ (longer/shorter) duration of action

Hydrophilic hormones not bound to plasma proteins have a ______ (longer/shorter) DOA

Free, longer (reservoir for slow release), shorter

Because hydrophobic hormones easily cross the plasma membrane, they have good ______ absorption and require ______ (more/less) frequent dosing

Oral, less

Because peptide/protein hormones are susceptible to degradation by GI enzymes, they must be given ______ (route).

Parenterally

The adrenal gland is divided into the ______ (outer) and ______ (inner).

cortex, medulla

The three zones of the adrenal cortex are ______, ______, and ______.

Zona glomerulosa, zona fasciculata, zona reticularis

The zona fasciculata synthesizes and secretes ______ hormones, specifically ______.

The zona glomerulosa synthesizes and secretes ______ hormones, specifically ______.

The zona reticularis synthesizes and secretes small quantities of the sex hormone precursor ______, which can be converted to ______ and ______ in peripheral tissues.

Glucocorticoid, cortisol, Mineralocorticoid, aldosterone, DHEA, estrogen, testosterone

The adrenal medulla synthesizes and secretes ______ and ______.

EPI, NE

The structure that controls cortisol release is called the ______.

Hypothalamic-Pituitary-Adrenal (HPA) axis

The hypothalamus releases ______ (abbreviation: ______)

Corticotropin Releasing Hormone, CRH

CRH acts on receptors on pituitary ______ to release ______, which is also known as ______.

Corticotrophs, ACTH, corticotropin

ACTH acts on receptors on ______ cells of the adrenal cortex to stimulate ______ synthesis and release

Zona fasciculata, cortisol

As cortisol levels increase, cortisol inhibits release of ______ and ______ — this is called a ______ feedback loop

CRH, ACTH, negative

ACTH and cortisol secretion peak at ______ (time of day) and are lowest at ______ (time of day)

Morning, midnight

The best sampling times for diagnosing Cushing syndrome are ______ plasma cortisol or ______ salivary cortisol

Midnight, late night

Cortisol binds to ______ receptors, causing a conformational change and nuclear translocation, leading to binding at the ______ region

GR, promoter (GRE)

Cortisol's effects on metabolism include ______, ______, and ______, leading to increased blood glucose, free fatty acids, and muscle weakness

Lipolysis, gluconeogenesis, protein breakdown

Cushing's syndrome caused by ACTH-secreting tumors is called ______ Cushing's syndrome

ACTH-dependent

Noncancerous tumors of pituitary corticotrophs are called ______, and this specific subtype is termed ______ — the most common cause, with higher incidence in ______ (males/females).

Pituitary adenomas, Cushing's disease, females

Cancerous tumors outside the pituitary that secrete ACTH (e.g., pancreas, thyroid, lungs) are called ______ ACTH-secreting tumors, with higher incidence in ______ (males/females).

Ectopic, males

Cushing's syndrome caused by cortisol-secreting tumors is called ______ Cushing's syndrome, which includes noncancerous ______ and cancerous ______

ACTH-independent, adrenal adenomas, adrenal carcinomas

______ Cushing's syndrome is caused by steroid intake

Iatrogenic

In ACTH-dependent Cushing's syndrome (Cushing's ______), both ACTH and cortisol are ______

Disease, increased

In ACTH-independent Cushing's syndrome (Cushing's ______), cortisol is ______ and ACTH is ______, due to negative feedback

Syndrome, increased, decreased

Addison's disease caused by adrenal destruction (autoimmune disorders, TB, or drug-induced) is called ______ adrenal insufficiency; the 4 causative drugs are ______, ______, ______, and ______

Primary, ketoconazole, phenytoin, phenobarbital, rifampin

Addison's disease caused by prolonged exogenous steroid use is called ______ adrenal insufficiency

Secondary

Cushing's symptoms due to altered lipid metabolism include ______, ______, ______, ______, and ______

Moon face, buffalo hump, truncal obesity, striae, dyslipidemia

Cushing's symptoms due to altered collagen/protein metabolism include ______ and ______.

Muscular weakness, thin skin prone to bruises

Cushing's symptoms due to altered glucose metabolism include ______ and ______

Glucose intolerance, insulin resistance

Cushing's symptom due to altered calcium metabolism: ______

Bone fractures

Cushing's symptoms due to effects on the brain: ______

Anxiety/mood changes

Cushing's symptoms due to mineralocorticoid activity: ______ and ______

Fluid retention, HTN

Cushing's symptom due to sex hormone activity: ______

Cushing's syndrome increases risk of ______ due to immunosuppression

Hirsutism, Infection

Biochemical changes in Cushing's syndrome include high /, high blood ______, and high plasma ______

Cortisol/ACTH, glucose, lipids

Addison's disease symptoms include ______ pigmentation of skin, changes in ______ distribution, GI disturbances, weakness, ______ (blood sugar change), ______ hypotension, and weight loss

Bronze, body hair, hypoglycemia, postural

An adrenal crisis includes profound fatigue, dehydration, ______ collapse, ______ shutdown, ______ (increased/decreased) serum Na, and ______ (increased/decreased) serum K.

Vascular (BP), renal, increased, decreased

The goal of pharmacologic management of Addison's disease is to correct ______ and ______ deficiency.

Glucocorticoid, mineralocorticoid

The 3 glucocorticoids used in Addison's disease are ______, ______, and ______; the mineralocorticoid used is ______

Hydrocortisone (cortisol), prednisone, cortisone, fludrocortisone acetate

The non-drug treatments for Cushing's syndrome are ______ of ACTH or cortisol secreting tumors, ______, or bilateral ______

Surgical resection, radiotherapy, adrenalectomy

Pharmacologic management is used in 3 situations: if ______ is not possible, as ______ treatment to decrease circulating cortisol, and as ______ treatment while awaiting the benefits of surgery

Resection, preoperative, postoperative

The 4 pharmacologic drug categories for Cushing's syndrome are: ______ inhibitors, ______, ______-receptor antagonists, and ______ of ACTH release

Steroidogenesis, adrenolytics, glucocorticoid, neuromodulators (DA receptor blockers)

The only FDA-approved steroidogenesis inhibitor for Cushing syndrome is ______, brand name ______

Osilodrostat, Isturisa

Osilodrostat's MOA is inhibition of the ______ enzyme (also known as ______) in zona fasciculata cells, blocking ______ synthesis

CYP11B1, 11-beta hydroxylase, cortisol

With osilodrostat, increased ______ levels lead to HTN and hypoK, while increased ______ levels lead to hirsutism and acne

Osilodrostat is metabolized hepatically by the enzyme ______

Mineralocorticoid, testosterone, CYP3A4

______ inhibits cortisol synthesis by inhibiting CYP enzymes (specifically ______) in zona fasciculata cells, and is the best tolerated and most effective drug in its class.

Ketoconazole, CYP17

______ is the adrenolytic DOC in cortisol-secreting adrenal carcinomas and is used in ACTH-independent Cushing's syndrome

Mitotane

Mitotane is a ______ selectively activated by adrenal cell CYPs to a toxic metabolite, thus selectively killing adrenal cells

Mitotane's MOA: Mitotane + adrenal CYPs → ______ → protein denaturation → ______ → less cortisol

Pro-toxin, Acyl Cl, cell death

______ (also called RU-486; brand name Korlym) is a glucocorticoid receptor antagonist that inhibits the biological effects of cortisol

Mifepristone

Cortisol levels ______ (increase/decrease/stay the same) with mitotane, osilodrostat, and ketoconazole, but ______ with mifepristone

Decrease, stay the same

The two neuromodulators that inhibit ACTH release are ______ and ______

Pasireotide, cabergoline

Pasireotide inhibits ACTH release via ______ receptor activation, while cabergoline inhibits ACTH release via ______ receptor activation

______ (brand name Signifor) is a long-acting somatostatin analogue, a peptide administered parenterally with high affinity for SST5 receptor subtypes

Mechanism-related SEs of pasireotide from SST receptor stimulation: GI tract → ______, ______, ______; pancreas → ______; pituitary thyrotrophs → ______

SST5, D2, Pasireotide, Diarrhea, abdominal pain, nausea, hyperglycemia, hypothyroidism