Endocrine Physiology Review Flashcards
The pituitary gland (hypophysis) is composed of:
Anterior pituitary = _________
Posterior pituitary = _________
Adenohypophysis [epithelial portion]
Neurohypophysis [neural portion]
Common presenting sign of cancers of the pituitary gland
Generally, cancers of the pituitary expand up into the brain and against optic nerves — often associated with dizziness and/or vision problems
The posterior pituitary is a collection of axons whose cell bodies are located in the _________ or _______ of the hypothalamus
Supraoptic nucleus (SON); paraventricular nucleus (PVN)
The posterior pituitary is a collection of axons whose cell bodies are located in the SON or PVN of the hypothalamus. What neuropeptides are primarily secreted in these nuclei?
ADH secreted mostly by SON
Oxytocin secreted mostly by PVN
The relationship between the hypothalamus and anterior lobe of the pituitary is both neural and hormonal. The anterior pituitary is a collection of endocrine cells that secretes what hormones?
ACTH TSH FSH LH GH Prolactin
[peptide hormones]
Differentiate between primary, secondary, and tertiary endocrine disorders
Primary disorders = abnormal hormone levels d/t defect in peripheral endocrine gland
Secondary disorders = abnormal hormone levels d/t defect in pituitary gland
Tertiary disorders = abnormal hormone levels d/t defect in hypothalamus
GHRH stimulates somatotrophs to release GH. What hormone inhibits somatotroph release of GH?
Somatostatin
__________ in the hypothalamus has an inhibitory effect on _______ in the anterior pituitary, preventing release of prolactin
PIF (dopamine); lactotrophs
Growth hormone is secreted from somatotrophs in a pulsatile manner. At what time of day is release of growth hormone the greatest?
Between midnight and 4am
Metabolic functions of growth hormone
Diabetogenic effects — increased BG concentration, resulting in increases in blood insulin levels
Increased protein synthesis and organ growth
Increased linear growth
The increased protein synthesis, organ growth, and linear growth due to growth hormone is mediated by __________
Somatomedins (IGF-1)
Growth hormone secretion is ______ in subjects who are malnourished or fasting
Increased
Most common cause of GH excess
Growth hormone-secreting pituitary adenoma
Consequences of GH excess before puberty vs. after puberty
Before puberty = gigantism
After puberty = acromegaly [increased periosteal bone growth, increased organ size, increased extremities size, coarsening of facial features, insulin resistance, and glucose intolerance]
How would the following change in order to trigger secretion of ADH:
Plasma osmolarity Blood pressure Blood volume Angiotensin II CNS stimulation Hydration status
Increased plasma osmolarity
Decreased BP
Decreased blood volume
Increased angiotensin II
Sympathetic stimulation
Dehydration
Secretion of ADH is MOST sensitive to changes in __________
Plasma osmolarity — an increase of only 1% in the osmolarity will increase ADH secretion
Central vs. nephrogenic diabetes insipidus
Central = lack of ADH [decreased plasma ADH] resulting from damage to pituitary or destruction of hypothalamus; can be treated with desmopressin
Nephrogenic = kidneys unable to respond to ADH [increased plasma ADH] resulting from drugs like lithium or chronic disorders (e.g., polycystic kidney disease, sickle cell anemia); CANNOT be treated with desmopressin
Results of water deprivation test in central vs. nephrogenic diabetes insipidus (in terms of urine osmolality post-desmopressin administration)
Central DI = urine osm increases
Nephrogenic DI = no change
Regions of the adrenal gland and hormones secreted
Capsule
Zona glomerulosa — mineralocorticoids (aldosterone)
Zona fasciculata — glucocorticoids (cortisol); androgens
Zona reticularis — glucocorticoids (cortisol); androgens
Adrenal medulla — catecholamines (E and NE)
All of the steroids that come from the adrenal gland are derived from _______ which is converted to pregnenolone via ___________
Cholesterol; cholesterol desmolase
Changes in mineralocorticoids, cortisol, androgens, BP, [K+], and androstenedione with a deficiency of 17alpha-hydroxylase
Increased mineralocorticoids
Decreased cortisol
Decreased androgens
Increased BP
Decreased [K+]
Decreased androstenedione
[may also present with undescended testes in males or lack of secondary sexual development in females]
Changes in mineralocorticoids, cortisol, androgens, BP, [K+], renin activity, and 17-hydroxyprogesterone with a deficiency of 21beta-hydroxylase
Decreased mineralocorticoids
Decreased cortisol
Increased androgens
Decreased BP
Increased [K+]
Increased renin activity
Increased 17-hydroxyprogesterone
[may also present with salt wasting, precocious puberty, or virilization]
Changes in mineralocorticoids, cortisol, androgens, BP, [K+], and renin activity with a deficiency of 11beta-hydroxylase
Decreased aldosterone, increased DOC
Decreased cortisol
Increased androgens
Increased BP
Decreased [K+]
Decreased renin activity
[may also present with virilization]
T/F: secretory rates of cortisol are high in the late evening
False — secretory rates of cortisol are high in the early morning but low in the late evening
Cushing’s syndrome vs. addison’s disease
Cushing’s syndrome = hypercortisolism
Addison’s disease = hypocortisolism
Cushing’s syndrome vs. cushing’s disease
Cushing’s syndrome = hypercortisolism d/t adrenal etiology (e.g., adrenal tumor)
Cushing’s disease = hypercortisolism d/t pituitary etiology (e.g., pituitary tumor)
Changes in plasma cortisol, plasma CRH, plasma ACTH, and hyperpigmentation with primary (adrenal) cortisol excess
Increased plasma cortisol
Decreased plasma CRH
Decreased plasma ACTH
No hyperpigmentation
Changes in plasma cortisol, plasma CRH, plasma ACTH, and hyperpigmentation with secondary (pituitary) cortisol excess
Increased plasma cortisol
Decreased plasma CRH
Increased plasma ACTH
YES hyperpigmentation
Changes in plasma cortisol, plasma CRH, plasma ACTH, and hyperpigmentation with primary cortisol deficiency
Decreased plasma cortisol
Increased plasma CRH
Increased plasma ACTH
YES hyperpigmentation
Changes in plasma cortisol, plasma CRH, plasma ACTH, and hyperpigmentation with secondary cortisol deficiency
Decreased plasma cortisol
Increased plasma CRH
Decreased plasma ACTH
No hyperpigmentation
________ has a direct stimulating effect on the ________ ______, mediating aldosterone release resulting in water/Na reabsorption and increased BP
Angiotensin II; adrenal cortex
3 cell types of islets of langerhans and the hormones they secrete
Beta cells — secrete insulin and peptide C
Alpha cells — secrete glucagon
Delta cells — secrete somatostatin
_______ is secreted from beta cells in equal amounts to insulin and is excreted unchanged in urine, thus it can be used to screen endogenous beta cell function
C peptide
Describe insulin receptor signaling
Insulin binding its tyrosine kinase receptor triggers the autophosphorylation of the receptor and phosphorylation of the family of insulin receptor substrate (IRS) and other substrate proteins
Substrate proteins in turn activate multiple downstream signaling cascades (e.g., PI3K and MAP kinase pathways) which mediate the metabolic and mitogenic activities of insulin — like increased glycogen/lipid/protein synthesis, decreased lipolysis, and cell growth/differentiation
Symptoms and diagnostic indicators of hypocalcemia
Hyperreflexia, spontaneous twitching (reduces threshold for AP), muscle cramps, tingling, numbness
Indicators: Chvostek sign, Trousseau sign
Symptoms of hypercalcemia
Decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness (decreased membrane excitability), hyporeflexia, lethargy, coma
T/F: Extracellular concentration of Pi is regulated by the same hormones that regulate Ca concentration
True
A decrease in plasma [Ca++] results in increased secretion of what hormone?
PTH
Effects of PTH on bone, kidney, and intestine
Bone — increased bone resorption —> increased plasma [Ca++]
Kidney — decreased Pi reabsorption (phosphaturia), increased Ca reabsorption, increased urinary cAMP —> increased plasma [Ca++]
Intestine — increased Ca absorption (indirect via vitamin D) —> increased plasma [Ca++]
What effect does chronic hypercalcemia have on PTH gene expression and secretion?
Causes decreased synthesis and storage of PTH, increased breakdown of stored PTH and release of inactive PTH fragment into the circulation
What effect does chronic hypocalcemia have on PTH gene expression and secretion?
Causes increased synthesis and storage of PTH and hyperplasia of parathyroid glands (secondary hyperparathyroidism)
PTH acts via what type of receptor?
GPCR
Main circulating form of vitamin D
25-OH-cholecalciferol
[main circulating form but has very low activity]
Enzyme responsible for converting 25-OH-cholecalciferol to the active form 1,25-dihydroxycholecalciferol in the renal proximal tubule
What are some activators of this enzyme?
1 alpha-hydroxylase (CYP1a)
Activated by decrease in [Ca], increase in PTH, or decrease in [Pi]
PTH receptors are located on osteoblasts NOT osteoclasts. What are the short-term actions vs. long-term actions of PTH on bone?
Short-term: bone formation (via direct action on osteoblast)
Long-term actions: increased bone resorption (indirect action on osteoclasts mediated by cytokines released from osteoblast)
Vitamin D increases Ca and Pi absorption in the small intestine by increasing _____ expression
Calbindin
Vitamin D promotes Pi reabsorption by proximal nephrons in the kidney by stimulating _____ expression; it has minimal actions on Ca in the kidney
NPT2a
Actions of vitmain D on parathyroid gland
Directly inhibits PTH gene expression
Directly stimulates CaSR gene expression
Changes in PTH, Ca, Pi, and vitamin D levels in primary hyperparathyroidism
Increased PTH
Increased Ca
Decreased Pi
Increased vitamin D
Define secondary hyperparathyroidism
Increase in PTH levels secondary to low [Ca] which may be d/t renal failure or vitamin D deficiency
Changes in PTH, Ca, Pi, and vitamin D levels in secondary hyperparathyroidism d/t renal failure
Increased PTH
Decreased Ca
Increased Pi
Decreased vitamin D
Changes in PTH, Ca, Pi, and vitamin D levels in secondary hyperparathyroidism d/t vitamin D deficiency
Increased PTH
Decreased Ca
Decreased Pi
Decreased vitamin D
Changes in PTH, Ca, Pi, and vitamin D levels in hypoparathyroidism
Decreased PTH
Decreased Ca
Increased Pi
Decreased vitamin D
Inherited autosomal dominant disorder in which Gs for PTH in bone and kidney is defective, resulting in hypocalcemia and hyperphosphatemia
Albrigt hereditary osteodystrophy [pseudohypoparathyroidism type 1a]
Changes in PTH, Ca, Pi, and vitamin D levels in pseudohypoparathyroidism type 1a [albright hereditary osteodystrophy]
Increased PTH
Decreased Ca
Increased Pi
Decreased vitamin D
Phenotype associated with pseudohypoparathyriodism type 1a
Short stature Short neck Obesity Subcutaneous calcification Shortened metatarsals and metacarpals
Changes in PTH, Ca, Pi, and vitamin D in humoral hypercalcemia of malignancy
Decreased PTH
Increased Ca
Decreased Pi
Decreased Vitamin D
Autosomal dominant disorder caused by mutations that inactivate CaSR in parathyroid glands and parallel Ca receptors in the ascending limb of the kidney resulting in decreased urinary Ca excretion and increased serum [Ca]
Familial hypocalciuric hypercalcemia (FHH)
Changes in PTH, serum Ca, urine Ca, Pi, and vitamin D with familial hypocalciuric hypercalcemia (FHH)
No change or increase in PTH
Increase serum Ca
Decrease urine Ca
No change in Pi or vitamin D
2 types of rickets
Pseudovitamin D deficient rickets (vitamin D-dependent rickets type I) — decreased 1 alpha hydroxylase
Pseudovitamin D deficient rickets (vitamin D-dependent rickets type II) — decreased vitamin D receptors
In terms of thyroid hormone synthesis, when availability of iodide is restricted, the formation of ____ is favored
T3
What is the wolff-chaikoff effect?
High levels of I- inhibit organification and synthesis of thyroid hormones
Most circulating thyroid hormone is ____, which has a half life of 6 days
T4
[T3 half life is 1 day]
Main thyroid hormone binding proteins
Thyroxine-binding protein (TBG) — higher affinity for T4 than T3
Transthyretin (TTR)
Albumin
Hepatic failure results in a decrease in blood TBG levels. How does this affect free thyroid hormone?
Transient increase in level of free T3, T4; followed by inhibition of synthesis of T3, T4 (negative feedback)
Pregnancy results in increased TBG levels. How does this affect free thryoid hormone?
Transient increase in bound T3, T4 (less free), eventually resulting in increased synthesis of T3,T4
[there is an overall increase in total levels of T3 and T4, but levels of free physiologically active thyroid hormones are normal — so person is said to be clinically euthyroid]
Most common cause of thyrotoxicosis
Graves disease [primary hyperthyroidism]
Condition in which thyroid hormone synthesis is impaired by thyroglobulin or TPO antibodies, which leads to decreased T3, T4 secretion…so TSH levels are high!
Hashimoto’s thyroiditis
A 41 y/o female presents with hyperphosphatemia, hypocalcemia, and decreased urinary Pi excretion. Injection of PTH leads to an increase in urinary cAMP. The most likely dx is:
A. Primary hyperparathyroidism B. Vitamin D intoxication C. Vitamin D deficiency D. Hypoparathyroidism after thyroid surgery E. Pseudohypoparathyroidism
D. Hypoparathyroidism after thyroid surgery
[Low blood Ca and high blood phosphate are consistent with hypoparathyroidism. Because the pt responded to exogenous PTH with an increase in urinary cAMP, the GPCR for PTH is normal, so pseudohypoparathyroidism can be excluded]
Which of the following acts on its target tissues by a steroid hormone MOA?
A. Thyroid hormone B. PTH C. ADH on collecting duct D. Beta1 adrenergic agonists E. Glucagon
A. Thyroid hormone
[thyroid hormone is an amine that acts on target tissues by a steroid hormone mechanism, inducing synthesis of new proteins]
Which step in steroid hormone synthesis, if inhibited, blocks the production of all androgenic compounds, but does not block glucocorticoid production?
A. Cholesterol —> pregnenolone
B. Progesterone —> 11-deoxycorticosterone
C. 17-hydroxypregnenolone —> dehydroepiandrosterone
D. Testosterone —> estradiol
E. Testosterone —> dihydrotestosterone
C. 17-hydroxypregnenolone —> dehydroepiandrosterone
[catalyzed by 17,20-lyase]
A 49 y/o female has hirsutism, hyperglycemia, obesity, muscle wasting, and increased circulating ACTH. The most likely cause of her sx is:
A. Primary adrenocortical insufficiency (Addison’s disease)
B. Pheochromocytoma
C. Primary overproduction of ACTH (Cushing’s disease)
D. Tx with exogenous glucocorticoids
E. Hypophysectomy
C. Primary overproduction of ACTH (Cushing’s disease)
Which of the following decreases the conversion of 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol?
A. A diet low in Ca B. Hypocalcemia C. Hyperparathyroidism D. Hypophosphatemia E. Chronic renal failure
E. Chronic renal failure
Increased adrenocorticotropic hormone secretion would be expected in pts:
A. With chronic Addison’s disease
B. With primary adrenocortical hyperplasia
C. Who are receiving glucocorticoid for immunosuppression after a renal transplant
D. With elevated levels of angiotensin II
A. With chronic Addison’s disease
[Addison’s disease is cuased by a primary adrenocortical insufficiency. The resulting decrease in cortisol production causes a decrease in negative feedback inhibition on the hypothalamus and anterior pituitary. Both of these conditions will result in increased ACTH secretion. Patients who have adrenocortical hyperplasia or who are receiving exogenous glucocorticoid will have an increase in the negative feedback inhibition of ACTH secretion]
Which of the following hormones acts by an IP3-Ca++ MOA?
A. 1,25-Dihydroxycholecalciferol B. Progesterone C. Insulin D. PTH E. GnRH
E. GnRH
Which step in steroid hormone synthesis is stimulated by ACTH?
A. Cholesterol —> pregnenolone
B. Progesterone —> 11-deoxycorticosterone
C. 17-hydroxypregnenolone —> dehydroepiandrosterone
D. Testosterone —> estradiol
E. Testosterone —> dihydrotestosterone
A. Cholesterol —> pregnenolone
Which of the following causes increased aldosterone secretion?
A. Decreased blood volume
B. Administration of an inhibitor of ACE
C. Hyperosmolarity
D. Hypokalemia
A. Decreased blood volume
Propylthiouracil (PTU) can be used to reduce the synthesis of thyroid hormones in hyperthyroidism because it inhibits oxidation of
A. T3 B. T4 C. DIT D. TSH E. Iodide
E. Iodide
[for iodide to be “organified” (incorporated into thyroid hormone), it must be oxidized to I2, which is accomplished by a peroxidase enzyme in the thyroid follicular cell membrane. PTU inhibits peroxidase and, therefore, halts the synthesis of thyroid hormones]
A 39 y/o man with untreated DM type I is brought to the ED. An injection of insulin would be expected to cause an increase in his:
A. Urine glucose B. Blood glucose C. Blood K+ D. Blood pH E. Breathing rate
D. Blood pH
Which of the following results from the action of PTH on the renal tubule?
A. Inhibition of 1alpha-hydroxylase
B. Stimulation of Ca-reabsorption in the distal tubule
C. Stimulation of Pi reabsorption in the proximal tubule
D. Interaction with receptors on the luminal membrane of the proximal tubular cells
E. Decreased urinary excretion of cAMP
B. Stimulation of Ca-reabsorption in the distal tubule
Which of the following pancreatic secretions has a receptor with 4 subunits, 2 of which have tyrosine kinase activity?
A. Insulin
B. Glucagon
C. Somatostatin
D. Pancreatic lipase
A. Insulin
