Endocrinology Flashcards
1
Q
Steroid hormones are derived from what?
A
Cholesterol
2
Q
What are amine hormones?
A
Hormones derived from tyrosine
3
Q
What are three examples of amine hormones?
A
Thyroid hormone
Epinephrine
Norepinephrine
4
Q
What hormones diffuse across the membrane and binds to the receptor in the cell?
(2)
A
Steroid hormones
Thyroid hormone
5
Q
The anterior lobe of the pituitary gland is linked to what? Via what structure?
A
To the hypothalamus via the hypothalamic-hypophysial portal system
6
Q
The posterior lobe of the pituitary is derived from what?
A
Neural tissue - Cell bodies located in the hypothalamic nuclei
7
Q
What are the hormones of the anterior lobe of the pituitary?
A
- Growth hormone
- Repro hormones (LH, FSH, prolactin)
- Thyroid-stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
8
Q
What are the products of proopiomelanocortin (POMC)?
A
- ACTH
- Melanocyte-stimulating hormone (MSH)
- B-lipoprotein
- B-endorphin
9
Q
What is a property of growth hormone release?
A
- Released in pulsatile fashion
10
Q
Growth hormone release is stimulated by:
A
- Sleep
- Stress
- Puberty
- Starvation
- Exercise
- Hypoglycemia
11
Q
Growth hormone release is decreased by:
A
- Somatostatin
- Somatomedins (insulin-like growth factor)
- Obesity
- Hyperglycemia
- Pregnancy
12
Q
How are somatomedins produced?
A
They are produced when growth hormone acts on target tissues. Then they inhibit further production of growth hormone.
13
Q
How does growth hormone act on the tissues?
A
- Via somatomedin (insulin-like growth factor or IGF) - produced in liver
- Direct effect of GH
14
Q
What are direct effects of growth hormone?
A
- Decreased glucose uptake into cells (diabetogenic)
- Increased lipolysis
- Increased protein synthesis (muscle/lean body mass)
- Increased production of IGF (somatomedin)
15
Q
What are the actions of growth hormone via IGF (somatomedin)
A
- Increased protein synthesis (chondrocytes)
- Increased linear growth (growth spurt)
- Increased organ size
- Increased lean body mass
16
Q
What does a growth hormone excess cause before and after puberty?
A
Before puberty - Gigantism
After puberty - Increased periostial bone, inc organ size, glucose intolerance
17
Q
What is octreotide? What does it do?
A
A somatostatin analogue - Inhibits growth hormone secretion
18
Q
What is the major hormone responsible for lactogenesis?
A
Prolactin
19
Q
What hormone inhibits prolactin?
A
Dopamine produced by hypothalamus
20
Q
What are the actions of prolactin?
A
- Milk synthesis
- Breast development
- Inhibit ovulation
21
Q
What are the hormones of the posterior lobe of the pituitary?
A
- Antidiuretic hormone (ADH)
- Oxytocin
22
Q
How are ADH and oxytocin produced?
A
Synthesized in the hypothalamic nuclei - then carried via axons to be secreted at posterior pituitary.
23
Q
Where is ADH specifically synthesized?
A
Supraoptic nuclei of hypothalamus
24
Q
Where is oxytocin originated?
A
Paraventricular nuclei of the hypothalamus
25
What is the effect of oxytocin?
Milk let-down
Uterine contraction
26
Which thyroid hormone is MORE biologically active?
T3 or T4?
T3
27
How does most of the T3 and T4 travel in blood?
Bound to thyroxine binding globulin (TBG)
28
How does hepatic failure affect thyroid levels?
Thyroxine binding globulin levels decrease - decreased total thyroid hormone - but normal levels of free hormone (clinically euthyroid)
29
Describe the hypothalamic-pituitary control of Thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH)
TRH - secreted by hypothalamus \> stimulates release of TSH by the anterior pituitary.
TSH then increases production of thyroid hormones
30
How does thyroid hormone negative feedback work?
T3 downregulates TRH receptors = decreased TSH release
31
What are thyroid-stimulating immunoglobulins?
IgG antibodies to TSH receptors - stimulate thyroid gland to secrete T3 and T4
32
How much more potent is T3 than T4
T3 is 4 times more potent than T4
33
What are the layers of the adrenal cortex? (from the outside in)
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticulosa
34
Where is aldosterone produced?
Zona glomerulosa
35
What does the zona fasciculata and zona reticularis produce?
Steroids and androgens
36
What are the layers of the adrenal cortex and what do they produce?
1. Zona glomerulosa (outermost layer) - Aldosterone
2. Zona Fasciculata (middle) - **Steroids** and androgen
3. Zona reticulata (innermost) - Steroids and **androgen**
37
Regarding adrenocortical hormone synthesis,
19-carbon steroids are:
Androgens; precursors to the estrogens
38
Regarding adrenocortical hormone synthesis,
18-carbon steroids are:
Estrogens
39
Regarding adrenocortical hormone synthesis,
21-carbon steroids are:
Everything else - Progesterone, deoxycortisone, aldosterone, cortisol
40
True or false: Glucocorticoid secretion oscillates with the circadian rhythm.
True
41
What are the effects of ACTH in the adrenal cortex? Via what enzyme?
Increased synthesis of all steroid hormones by stimulating *cholesterol desmolase*
42
What are the effects of chronic ACTH?
Increased up-regulation of ACTH receptors \> hypertrophy of adrenal cortex
43
Describe the hypothalamic control for corticotropin-releasing hormone (CRH)?
When neurons of the paraventricular nuclei (hypothalamus) are stimulated, CRH is released to the anterior pituitary =\> stimulates POMC and secretion of ACTH
44
How does cortisol provide negative feedback to the hypothalamus?
Cortisol inhibits CRH secretion from hypothalamus = decreased ACTH production
45
Where does angiogensin II work to stimulate aldosterone release?
Zona glomerulosa of the adrenal cortex
46
How do glucocorticoids exert their anti-inflammatory effects?
1. Induce synthesis of lipocortin - Inhibitor of phospholipase A2
2. Inhibit production of IL-2
3. Inhibit release of histamine/serotonin
47
How do steroids suppress immune response?
Inhibit production of IL-2 and T lymphocytes (cellular immunity)
48
How does cortisol cause hypertension?
1. Up-regulates a1 receptors on arterioles.
2. Mineralocorticoid effects - increased volume
49
How is ketoconazole used for treatment of Cushing's?
Inhibits steroid hormone synthesis
50
What is Conn's syndrome?
Hyperaldosteronism by an aldosterone-secreting tumor
51
What are the clinical findings in Conn's syndrome?
1. Hypertension
2. Hypokalemia
3. Decreased renin
52
21B-hydroxilase is involved in production of which 2 hormones?
1. Cortisol
2. Aldosterone
53
What findings are associated with 21B-hydroxylase deficiency?
1. Decreased cortisol and aldosterone levels
2. Increased progesterone and androgens
3. Increased ACTH (no negative feedback)
4. Hyperplasia of zona fasciculata and reticularis (increased ACTH)
54
What is the endocrine portion of the pancreas?
Islets of Langerhans
55
What is the major stimulus for glucagon secretion?
Decreased blood glucose
56
What are the general effects of glucagon?
1. Increased blood glucose concentration
2. Increases blood fatty acid and ketoacid concentration
3. Increases urea production (needed for amino acid production)
57
What do the beta cells of the pancreas do?
Secrete insulin
58
What do the alpha cells of the pancreas do?
Secrete glucagon
59
What do the Delta cells of the pancreas do?
Secrete somatostatin and gastrin
60
What is the C-peptide?
Product of the cleavage of proinsulin
Packaged and secreted along with insulin - used to monitor beta cell function in DM patients
61
How does glucose stimulate insulin secretion?
1. Glucose binds to **Glut 2** on beta cells.
2. K+ channels close \> depolarization of beta cells.
3. Depolarization opens Ca+ channels
4. Increased intracellular Ca+ leads to insulin release
62
How do the insulin receptors work on the target cells?
1. Beta subunit have intrinsic tyrosine kinase activity. And becomes intracellular once it is activated by insulin.
Therefore insulin down-regulates its own receptors in target cells
63
The number of insulin receptors are (increased/decreased) in starvation, and (increased/decreased) in obesity.
1. Increased
2. Decreased
64
What are the effects of somatostatin? (secreted by delta cells of pancreas)
Inhibits insulin, glucagon and gastrin secretion
65
What percentage of the total blood calcium is bound to protein?
40% is bound to plasma protein
66
What percent of total blood calcium is not bound to protein?
60%
67
What is ultrafiltrable calcium?
Non-protein bound calcium:
1. Ca2+ complexed to anions (e.g. phos)
2. Free ionized calcium (biologically active)
68
What cells produce and secrete PTH?
Chief cells of the parathyroid gland
69
What are the effects of PTH on bone?
Increased bone resorption (Calcium and phosphorus released to blood) via hydroxyproline excretion
70
Patients with increases in PTH-rp will have (high/low) PTH levels?
Low due to feedback inhibition from high serum Ca+
71
Vitamin D deficiency in children causes:
Rickets
72
In adults, vitamin D deficiency causes?
Osteomalacia
73
What is the active form of vitamin D?
1,25-dihydrocycholecalciferol (calcitriol) - formed by the enzyme 1a-hydroxylase
74
What is the overall effect of calcitriol on calcium and phosphate?
Increase both
75
What cells secrete calcitonin?
Parafollicular cells of the thyroid
76
How does calcitonin work?
Inhibits bone resorption
77
Most of the cholesterol (80%) used for synthesis of steroid is provided by what?
Low-density lipoprotein (LDL)
78
How is cortisol carried in blood? (2 proteins)
Cortisol-binding globulin \>\>\>\> albumin
Very small portion is free (\*active form\*)
79
What percentage of patients with Cushing's have PDH?
80-85%
80
What are the more common kinds of PDH tumors?
Pars distalis tumor in 75% of cases
Pars intermedia tumor in 25% of cases
81
When screening a clinical dog for Cushing's with a LDDST, which cortisol is diagnostic (baseline, 4h, 8h)
Cortisol at 8h
82
What percentage of dogs with PDH will suppress at the 4h cortisol?
30%
83
What is the cut-off value of cortisol for suppression?
\<1.4 ug/dL or 40nmol/L
84
In an LDDST, what does an escape from suppression at the 8 hour cortisol tell you?
Diagnosis of PDH
85
What is the sensitivity of LDDST for diagnosis of Cushing's?
**Sensitivity 85%-100%**
Specificity 44-73%
86
What test is best to identify iatrogenic Cushing's?
ACTH stim
87
What is the sensitivity and specificity of ACTH stim for diagnosis of Cushing's?
Sensitivity 60-85%
## Footnote
**Specificity 85-90%**
88
ACTH stim vs. LDDST - Which one is sensitive, which one is specific?
LDDST - Sensitive
ACTH stim - Specific
89
How do dogs with Cushing's respond to ACTH stim? What about iatrogenic cushing's?
Dogs with Cushing's - Exaggerated cortisol elevat
Dogs with Iatrogenic cushing's - No increase in cortisol
90
What test is used to monitor for treatment response in Cushing's?
ACTH stim (lower dose used)
91
Which thyroid hormone has the shortest latency period and is the quickest to reach maximum cellular activity?
T3
92
What insulin-dependent glucose transporter (GLUT) is found in fat and muscle?
GLUT 4
93
What percentage of the pancreas is exocrine and what percentage is endocrine?
Exocrine - 80%
Endocrine 20%
94
What is the general cause of diabetes mellitus in dogs vs. cats?
Dogs - Immune destruction of beta cells, vacuolar degeneration or pancreatitis.
Cats - Islet cell amyoidosis
95
What are the two types of DM?
Type 1 DM - Beta cell destruction w/ absolute insulin deficiency. Dogs mostly
Type 2 DM - Defect in insulin secretion/insulin resistance. Cats mostly
96
Do cats with diabetes mellitus get cataracts?
No
97
What is the ideal diet for cats with diabetes mellitus?
High protein with limited carbohydrate intake
98
ADH is produced by which nuclei?
Supraoptic nuclei
99
Oxytoxin is produced by which nuclei?
Paraventricular nuclei
100
What is the difference in the etiology of acromegaly in dogs and cats?
Cats - Secondary to pituitary tumor
Dogs - Usually exogenous or endogenous (ovaries) progestins that stimulate GH secretion from mammary tissue. Tx - spay
101
What is contained within the follicles of the thyroid gland?
Contain colloid, most of which is thyroglobulin
102
What is the essential building block of thyroglobulin?
Tyrosine
103
What does thyroglobulin contain?
T4, T3, mono- and diiodotyrosine
104
What is the effect of thyroid hormone on the myocardium?
Stimulates production of myosin isoform that speeds the interaction between myosin and actin = increased rate of contraction
105
What is a mechanism for thyroid autoregulation?
Wolff-Chaikoff mechanism - increasing iodide slows the rate of thyroid hormone synthesis.
106
How does hyperthyroidism cause vomiting?
Thyroid hormone stimulates CRTZ
107
What is primary hypoadrenocorticism? Is the plasma ACTH low or high?
* Adrenal deficiency
* More than 95% of cases
* Plasma ACTH is high
108
What is secondary hypoadrenocorticism?
* Decreased ACTH production
* Commonly caused by excess steroid administration
109
What causes primary hypoadrenocorticism?
* Immune-mediated destruction
* Mitotane or trilostane treatment
* Bilateral adrenalectomy
110
Why does primary addison's cause skin hyperpigmentation in people?
Increased ACTH production leads to increased production of a-melanocyte stimulating hormone (a-MSH)
111
Feline hypersomatotropism is secondary to neoplastic transformation of which cell type?
Acidophil (Somatotrophs)
112
MOA: Diazoxide
(Medication for hyperinsulinism) Direct vasodilator to peripheral arteriole smooth muscle. Directly inhibits pancreatic insulin secretion, stimulates hepatic gluconeogenesis and glycogenolysis, and stimulates beta-adrenergic system to cause ephinephrine release and inhibit tissue use of glucose.
113
MOA: Pamidronate, Zoledronate
Biphoshonates - Inhibit bone resorption by binding to hydroxyapatite crystals. Impede osteoclast activity
114
MOA: Methimazole
Inhibits thyroid peroxidase and interferes with iodine incorporation into tyrosyl residues of thyroglobulin, thereby inhibiting thyroid hormone synthesis.
115
MOA: Desoxycorticosterone Pivalate (DOCP)
Long-acting mineralocorticoid. Acts at the renal distal tubule where it increases absorption of sodium. Also enhances potassium and hydrogen excretion.
116
MOA: Octreotide
Long-acting somatostatin analog. Inhibits synthesis and secretion of insulin, glucagon, secretin, growth hormone, gastrin, and motilin.
117
MOA: Desmopressin
Similar vasopressin, but has more antidiuretic activity and less vasopressor properties.
Also increases plasma factor VIII and plasminogen factor (tx for vWD)
118
What are symptoms of acromegaly in dogs?
Soft tissue swelling of face and neck
Hypertrophy of tongue, pharynx
Organomegaly
Hyperglycemia
119
Thyroid works on what kind of receptors?
Nuclear receptors
120
How does thyroid hormone affect the heart muscle?
Stimulates production of myosin, increasing rate of contraction
121
What is the primary source of cholesterol for the synthesis of adrenocortical hormones?
LDL
122
What is the rate limiting step in production of adrenocortical hormones?
Cholesterol \> Pregnenolone
Catalyzed by cholesterol desmolase
123
Increased aldosterone leads to what acid/base status?
Metabolic alkalosis
124
Insulin stimulates translocation of what receptor to the membrane?
GLUT-4
125
What causes nutritional secondary hyperparathyroidism?
Diets low in calcium or vitamin D
Diets excessive in phosphorus
126
What are the results of nutritional secondary hyperparathyroidism?
Increased bone resorption - osteopenia
Lamenes, limb deformity, fracture, ect
127
What acid base status worses hepatic encephalopathy?
Alkalosis - causes more ammonia to be absorbed into CNS
128
What electrolyte disturbance worsens hepatic encephalopathy?
Hypokalemia
129
ALP elevations in cats are sensitive/specific? why?
Specific (cholestasis)
Cats do not have steroid isoenzime
130
How is ALP cleaved in order for it to go into the bloodstream?
Cleaved by:
Bile acids
phospholipase D
Proteases
131
What insulin is long acting due to the formation of crystals SQ?
Glargine
132
What insulin is long acting by causing slowly reversible binding to albumin?
