Physio Flashcards
1
Q
What effect does GLP-1 (incretin) have on insulin release?
A
Increases insulin release in the B cells of the pancreas
Degraded by DPP-IV, so DPP-IV inhibitors help to incr GLP-1 in Type 2 DM
2
Q
TQ
What are the causes of elevated blood glucose in type 2 DM? (3 due to obesity)
A
- Combo of insulin resistance and deficiency
- Decr GLUT-4 uptake of glucose in response to insulin
- Decr ability of insulin to repress hepatic glucose production
- Inability of insulin to repress hormone-sensitive lipase (HSL) or increase lipoprotein lipase (LPL) in adipose tissue
Also: decr GLP-1
3
Q
What is the pathophysiology of type 1 DM, both immunologic and metabolic?
A
Immuno:
-Absolute deficiency of insulin secretion due to B-cell destruction by islet auto-ab
Metabolic:
-Decreased glucose transport into cells by GLUT4
-Increased glucose production (glycogen, gluconeogenesis)
-Incr activity of hormone sensitive lipase (FFA and ketones made)
4
Q
- Early onset (childhood)
- Dehydrated with polydispia, polyuria, wt loss, fruity breath
- Cool clammy skin with rapid shallow breathing
- Dry skin and mucous membranes
- No fam hx
- Hyperglycemia
- ketoacidosis
- High anion gap
A
Type 1 DM (ketoacidosis)
Tx: IV fluids–>insulin–>decr K so electrolyte replacement
5
Q
- Late onset
- Genetic (fam hx)
- Obese
- Hyperglycemia
- Hyperlipidemia
- A1c 8.4% (>6.5%)
A
Type 2 DM
6
Q
The following hormones are released by which endocrine gland? TRH CRH GnRH GHRH Somatostatin Dopamine
A
Hypothalamus
7
Q
The following hormones are released by which endocrine gland? TSH FSH LH ACTH GH Prolactin
A
Anterior pituitary
8
Q
The following hormones are released by which endocrine gland?
Oxytocin
ADH
A
Posterior pituitary
9
Q
The following hormones are released by which endocrine gland?
T3, T4
Calcitonin
A
Thyroid
10
Q
The following hormones are released by which endocrine gland?
PTH
A
Parathyroid
11
Q
The following hormones are released by which endocrine gland?
Inuslin
Glucagon
A
Pancreas
12
Q
The following hormones are released by which endocrine gland?
Norepi
Epi
A
Adrenal medulla
13
Q
The following hormones are released by which endocrine gland?
Renin
1,25-dihydroxycholecaliferol
A
Kidney
14
Q
The following hormones are released by which endocrine gland?
Cortisol
Aldosterone
Adrenal androgens
A
Adrenal cortex
15
Q
The following hormones are released by which endocrine gland?
Testosterone
A
Testes
16
Q
The following hormones are released by which endocrine gland?
Estradiol
Progesterone
A
Ovaries AND
Corpus luteum
17
Q
What is insulin’s structure?
What is the significance of C peptide as a diagnostic value?
A
Insulin is a peptide hormone and therefore requires 2 cleavages (preprohormone–>prohormone–>hormone)
This takes longer to synthesize.
Anytime C peptide=insulin release
18
Q
What is the effect of insulin on glucose uptake and carb metabolism in muscle, liver, brain, and adipose tissue?
A
- Stimulates glucose uptake by skeletal m. & adipose tissue
- Incr glycogen storage in liver & skeletal m.
- Suppresses glucose output by liver
- Promotes TG synthesis and storage in liver & adipose tissue
- Promotes clearance of chylomicrons from blood
- Suppresses lipolysis of adipose TG stores
19
Q
What is the effect of insulin on fat and protein metabolism?
A
Low insulin–>decrease breakdown
High insulin–>increase formation
20
Q
What is the effect of insulin on serum potassium?
A
Majority of potassium excretion occurs in kidney is determined on aldosterone-renin-angiotensin pathway.
Insulin promotes movement of potassium into the intracellular space
21
Q
What is the relationship between ketosis to insulin-deficiency?
What is ketoacidosis?
A
Insulin deficiency--> Incr lipolysis--> Incr FFA to liver--> Incr ketogenesis--> Increase ketoacidemia--> Incr acidosis
Also: Hyperglycemia--> Osmotic diuersis--> Decr renal fx--> Acidosis
22
Q
What are the effects of glucagon on blood glucose concentrations?
A
Increases blood glucose
23
Q
What promotes and suppresses both insulin and glucagon secretion?
A
Glucose stimulates insulin secretion by β-cells and suppresses glucagon from α-cells (via catecholamines)
24
Q
What do patients with type 1 and type 2 DM have in common?
A
Nonenzymatic glycosylation of proteins
25
In type __ DM, there is reduced incretin effect, meaning that there is decreased release of GLP-1
2
26
Fasting glucose over ___ and 2 hr oral glucose (75 mg) tolerance test over ___=diabetes
126
| 200
27
What can be administered to raise blood glucose during hypoglycemic event?
glucagon
28
How does GH and gonadotropins influence insulin?
Block insulin so since high GH at night then high glucose in evenings (low insulin)
29
In a ketoacidotic diabetic pt, C peptide would likely be at ___ng/mL (normal 0.5-2.5)
0
| no insulin
30
- Ischemic infarct of pituitary following postpartum bleeding
- Usually presents with failure to lactate, absent menstruation (amenorrhea), cold intolerance
- Hypopituitarism (all hormones are low compared to reference range)
Sheehan syndrome
31
What are pregnant women susceptible to pituitary infarction?
Incr lactotropes >>
Incr size of anterior pituitary without corresponding incr in blood supply >>
Ischemia >> necrosis
32
In some cases of Sheehan syndrome the posterior pituitary is relatively unaffected. How can you explain this finding?
Posterior pituitary has a direct blood supply.
33
- Motorcycle accident causes concussion; pt has not felt the same since accident
- Pt is fatigued, gained 5 lbs, and drinks and urinates more than before the accident
- PE: Galactorrhea, otherwise healthy
- All lab values are low, except for prolactin (> 3x reference range)
What is the cause of the pt's hyperprolactinemia?
A. Ischemic necrosis of the pituitary
B. Traumatic damage to the pituitary stalk
C. Prolactinoma‐ adenoma of the lactrotropes
D. Increased prolactin secretion due to use of a dopamine antagonist
E. Hypothyroidism
B. Traumatic damage to the pituitary stalk
34
* cc: Megan is a 30 y/o female who is seen by her gynecologist for irregular menses and missed periods.
* Hx: She is not currently taking any form of hormonal birth control and she and her husband have relied on barrier methods for contraception. Prior to the past year, her menses have been regular. Onset of menarche was at a normal age.
* PE: Megan’s pelvic examination was normal.
Lab values:
- Pregnancy test: Negative
- FSH: 2 mIU/ml (nl, 4‐30)
- LH: 2 mIU/ml (nl, 5‐30)
- Cortisol (4 PM): 7
C. Prolactinoma‐ adenoma of the lactrotropes
Rx: Bromocriptine (dopamine agonist, which inhibits prolactin secretion)
35
In hyperprolactinemic states you can expect to see low levels of gonadotropins (FSH and LH). Why?
High prolactin levels inhibit GnRH secretion, which will decrease levels of FSH and LH.
36
- Excess GH in adults
| - Typically caused by pituitary adenoma
Acromegaly
37
Name a few factors which STIMULATE GH secretion.
- Fasting
- Stress
- Amino acids
- Hypoglycemia
38
Name a few factors which SUPPRESS GH secretion.
- Obesity
- High FFA
- Hyperglycemia
- Hypothyroidism
- IGF-1
39
Name a few factors which INHIBIT GH secretion.
- Acute and chronic illness
- GH receptor deficiency
- GHR antibodies
- IGF-1 receptor deficiency
40
Case:
- Deepened skin creases
- Thickened skin
- Bulbous nose and lips
- Jaw appeared more prominent
- Hands were bulky
- Optic nerves were slightly atrophied
* Pt's fasting GH level was elevated at 56 ng/ml (normal 0‐5 ng/ml).
* Pt's IGF‐1 (also known as somatomedin C) level was 988 ng/ml (normal 90‐360 ng/ml).
* A oral dose of 100 g of glucose syrup was given. Normally this dose would suppress GH levels to s were 43 ng/ml.
* The physical changes and the bitemporal hemianopsia are consistent with excess growth hormone (acromegaly).
What would you expect to find on MRI?
Why was pt given a glucose suppression test?
Macroadenoma in the pituitary gland that compressed the optic nerve.
Pt was given a glucose suppression test because hyperglycemia suppresses GH. In this case the glucose did not decrease... Therefore an MRI needed to be ordered, which revealed a pituitary mass, causing acromegaly.
41
A woman was scheduled for a growth hormone suppression test. If each of the following events occurred the morning of the test, which of the events would be most likely to suppress growth hormone levels?
a. She ate four large doughnuts for breakfast.
b. While unlocking her car, she was chased by the neighbor’s vicious dog.
c. She fell asleep at the start of the test and slept soundly until it was completed 1.5 hours later.
d. She forgot to eat her breakfast before the test.
a. She ate four large doughnuts for breakfast.
Hyperglycemia suppresses GH secretion.
42
How does GH affect insulin sensitivity?
GH impairs glucose tolerance, causing insulin resistance.
| ß-cells of pancreas become exhausted >> insulin deficiency
43
What are a few therapeutic strategies for acromegaly caused by a GH-secreting tumor of the anterior pituitary?
- Surgical resection of pituitary adenoma
- Rx: octreotide (somatostatin analog)
- Rx: pegvisomant (GH receptor antagonist)
44
Summary of GH actions:
1. Diabetogenic effect‐ causes insulin resistance
- glucose uptake
- blood glucose levels
- lipolysis
- blood insulin levels
2. Increased protein synthesis and organ growth (through the actions of IGF‐I)
- amino acid uptake
- DNA, RNA, protein synthesis
- Lean body mass and organ size
3. Increased linear growth (through the actions of IGF‐I)
- Cartilage metabolism?
```
1. Diabetogenic effect‐ causes insulin resistance
↓ glucose uptake
↑ blood glucose levels
↑ lipolysis
↑ blood insulin levels
```
2. Increased protein synthesis and organ growth (through the actions of IGF‐I)
↑ amino acid uptake
↑ DNA, RNA, protein synthesis
↑ lean body mass and organ size
3. Increased linear growth (through the actions of IGF‐I) Altered cartilage metabolism
45
```
Administration of thyroid hormone to a patient with hypothyroidism will have which effect?
A. Increase TSH levels
B. Decrease TSH levels
C. Decrease iodide uptake by the thyroid
D. Increase thyroglobulin levels
E. Induce thyroid gland hyperplasia
```
B. Decrease TSH levels
Incr TH--> Decr TSH due to negative feedback
```
Why not C?
Iodine def-->
Give iodine-->
Incr uptake-->
Incr TH
```
46
What are the relations b/t metabolic actions of thyroid hormone and the clinical presentation of hypothyroidism and hyperthyroidism?
Hypofunction:
- Loss of hair, coarse/brittle hair
- Periorbital edema
- Puffy face
- Normal or small thyroid
- HF (bradycardia)
- Constipation
- Cold intolerance
- Muscle weakness
- Edema of extremities
Hyperfunction:
- Thin hair
- Exophthalmos
- Enlarged thyroid: diffuse (warm), Nodular, Solitary (toxic)
- HF (tachycardia)
- Wt loss
- Diarrhea
- Warm skin w/ sweaty palms
- Hyperreflexia
- Pretibial edema
47
What are the characteristics of Grave’s disease?
Hyperthyroid:
- Bulging eyes
- Thin
- Tremors
48
What are the characteristics of Hashimoto’s thyroiditis?
Hypothyroid:
- Edema
- Puffiness
- Wt gain
- Cold
- Goiter
- Skin changes
- Constipation
- HA
- Fatigue
- Anovulation
49
How do the physical changes in the thyroid gland (assessed by palpitation) correlate to different pathologies in hypothyroid and hyperthyroidism
Normal or small or painful=hypothyroid
Englarged (diffuse (warm), Nodular, Solitary (toxic)=hyperthyroid
50
How do changes in thyroid‐binding protein alter total T4 levels?
Ex: pregnancy
High thyroxine binding globulin leads to high T3 but no effect on free T4
51
A 24 y/o pregnant women and her 3 y/o child are seen in a medical mission clinic in the Sudan. The child is short in stature, has a potbelly, enlarged protruding tongue, and is developmentally delayed. Iodine is prescribed for mother and child. In the absence of iodine during fetal development, biosynthesis of which hormone is inhibited resulting in the child’s presentation?
```
A. Insulin
B. Cortisol
C. Growth hormone
D. Thyroid hormone
E. IGF‐I
```
D. Thyroid hormone
Decr thyroid-->mental delays
Notes:
Thyroid hormone is essential for normal growth and development:
52
What is included in a thyroid function test and which value is the most reliable for thyroid function?
- Serum thyroxine (total T4) is influenced by the amount of hormone and the amount of TBG
- Free T4 (difficult to measure accurately)
* *-Serum TSH is the most reliable
53
T/F:
| TRH is included in a thyroid test
FALSE
| TRH is not in the serum! Acts on ant. pituitary and no systemic presence
54
What lab values do we see in hyperthyroid? (↑/↓)
TSH
T4
↓TSH
| ↑T4
55
- AutoAb mimic/stimulate TSH (TSAb) & activate TSHR
- Women 20-40
- Enlargement of thyroid gland
- -↑T4 T3 -->↓TSH
- **Infiltrative ophthalmopathy with exophthalmos (due to inflam)
- Localized, infiltrative dermopathy (pretibial myxedema...edema around shins)
What is the treatment?
Grave's disease
(Autoimmune hyperthyroid disease)
Tx:
- Block thyroid function
- Gland removal (radioactive ablation-->hypothyroid-->give thyroid replacement)
- Less effective: immune supp, Ab clearance
56
- Exogenous thyroid hormone
- Gland atrophy
- Low thyroglobulin
```
Factitious thyrotoxicosis (hyperthyroid)
-Tx too high (↓ thyroid fx) Ex: hasimotos
```
57
- "Hot nodule"
- Overprod of thyroid
- ↓TSH
- Gland atrophy around nodule
Toxic adenoma
58
- Granulomatous
- Viral
- Painful gland
- Transient cycles of hyperthyroid, euthyroid, hypo thyroid, euthyroid
Subacute thyroiditis
59
- Subacute lymphocytic
- Autoimmune
- non-tender gland
- Transient cycles of hyperthyroid, euthyroid, hypo thyroid, euthyroid
- Postpartum?
Silent thyroiditis
60
What is the one clinical exception to hyperthyroidism having ↓TSH?
pituitary overproduction of TSH
61
In hyperthyroid, there is (↑/↓) absorption of radioactive iodine by the thyroid and an (↑/↓) of radioactive iodine in the urine
Thyroid gland uses iodine to make TH...
Incr. absorp
Decr. in urine
Opposite for hypothyroid!
note: can also do radioactive thyroid scans
62
For the following hypothyroidisms, where is the point of interruption?
Primary
Secondary
Tertiary
Primary=thyroid gland (hasimotos or thyroid ablation)
Secondary=pituitary insuff
Tertiary=hypothalamic disease
63
- T cell mediated disease with some autoab against thyroglobulin, thyroid peroxidase, TSHR, and iodine transporter
- Women 46-65
- Clusters in families
- Inflam of thyroid gland w/ gradual thyroid failure-->fatigue with wt gain
Hasimotos thyroiditis
64
What is the most common disorder of hypothyroidism in iodine sufficient areas?
Hasimotos thyroiditis
65
Pt presents w/...
- Goiter
- skin change
- peripheral edema
- constipation
- headache
- fatigue
- anovulation
↑TSH and TRH
↓T3 and T4
Tx?
Replacement therapy with levothyroxine (T4)
66
Thyroid hormone (T3 T4) synthesis steps?
```
Thyroid follicular cell
-Syn of TGB-->
Colloid by exocytosis
-TGB + Iodine-->
-MIT and DIT (T3, T4)-->
Thyroid follicular cell via pinocytosis
-Proteolysis-->
Releases T3 and T4 into blood
Recycling of TGB, iodine
```
67
The absence of iodine for an extended period of time will result in which changes to thyroid laboratory values?
(TSH, Total T4, Total T3)
↓T3 and T4 --> ↑TSH
68
Karen is a 35 year‐old female who complains of sweating, palpitations and a 15 lb weight loss over the past two months. Her vital signs are P 110, RR 15, BP 145/95, and T 37°C. On physical exam there is a small goiter
Testing shows a suppressed TSH and an increased homogeneous radioactive iodine uptake. Which finding would be likely in the patient?
A. Surreptitious use of thyroid hormone
B. A painful thyroid gland
C. Elevated thyroid stimulating immunoglobulins
D. A low T3
E. A high thyroxine binding globulin (TBG)
C. Elevated thyroid stimulating immunoglobulins (graves)
A. Incr iodine uptake so NOT an option)
B. Painful is hypo
D. Hyperthyroid so incr T3
E. High TBG is in pregnancy...high T3 but normal T4...
69
Pt treated with hyperthyroid due to graves with radioactive iodine. Felt great for a few months but presents with lethargy and fatigue. ..
What lab values expected? (TSH, T3, T34
Decr T3 T4
Incr TSH
Hypothyroid! Due to iodine-->
Fatigue, constip, cold hands and feet
70
On exam of hypothyroid treated pt due to radioactive iodine presenting with sweating, palpitations, and wt loss, you notice lid lag, tremor and a fast pulse. A blood test shows a suppressed TSH level of 0.03.
What additional findings on physical exam would be present in each of the following possibilities?
– Recurrence of hyperthyroidism
– Over‐replacement with thyroid hormone
What tests may be helpful in establishing the diagnosis in each case?
Reoccurrence: wt loss, anxiety, brittle hair, diarrhea, incr gland size
Over-replacement: gland atrophy (ablation with radioactive)
Iodine radioactive scan is helpful!
71
Josephine is 28 years old and comes to see you for a checkup 4 months after an uneventful pregnancy. She was seen by her obstetrician 6 weeks after delivery. At that time she felt tired and was not sleeping well, which she attributed to having to wake up frequently to breast‐ feed her baby. She lost all the weight she had gained during the pregnancy, and also noticed marked hair loss. In the last couple of weeks she has been sleeping better but has been even more fatigued, and now complains of constipation. On exam, you notice a small goiter, delayed relaxation of the deep tendon reflexes and dry skin. You suspect that she has a thyroid problem and you order a TSH level, which is high at 15 mIU/L (normal 0.5‐5).
a) What is the most likely diagnosis?
b) Is a radioactive iodine scan helpful in this situation?
c) What treatment may be offered to this patient?
a) Hashimoto's or silent thyroiditis (post-partum)
b) NO also contraindicated if breast feeding
d) What treatment may be offered to this patient? Follow pt or give thyroid hormone
72
cc: Mrs. Omaya has been fatigued since giving birth 9 months ago.
Hx: She had been in good health up to and throughout the pregnancy (her second). She was able to nurse for only 1 month because her milk production was scant. She has not begun menstruating again since the delivery. She has been unable to lose the weight she gained during her pregnancy. She also notes that her skin has become rough and her voice deeper since the birth of her child. Mrs. Omaya’s delivery was difficult and she required a blood transfusion with 6 units of blood.
VS: T 37C, BP 100/70 mm Hg, P 60/min
PE: a coarse skin texture was present; physical exam otherwise normal.
Labs: all pituitary hormones decreased!
```
Mrs. Omaya has low T4 and TSH. How would you classify her thyroid deficiency?
A. Primary hypothyroidism
B. Secondary hypothyroidism
C. Tertiary hypothyroidism
D. Tissue resistance to thyroid hormone
```
B. secondary hypothyroidism (no pituitary)
73
```
TQ
A 35 y/o female presents with galactorrhea, amenorrhea, headaches, fatigue, and weight gain. Laboratory evaluation reveals the following:
-Prolactin 58 ng/ml (nl, 2‐ 25)
-Free T4 0.2 ng/dL (nl, 4.5‐12)
-TSH 100 mU/L (nl, 0.5‐ 5.0).
She has an enlarged pituitary gland on MRI scan. What is the probable diagnosis?
A. Prolactinoma
B. Hypothyroidism
C. Silent thyroiditis
D. Thyrotroph adenoma
E. Median eminence laceration
```
B. Hypothyroidism (decr T4-->incr TSH and Incr TRH-->Incr prolactin)
NOT
A. Prolactin >200 and no change in TSH
D. ↑TSH-->↑T3,4, no change in prolactin)
74
A 39 y/o HIV‐positive male with Pneumocystis carinii pneumonia has the following serum thyroid hormone values:
-T4 = 4.0 μg/dL (nl, 4.5‐12.0)
-T3 = 60 ng/dL (nl, 90‐200)
-TSH = 1.3 mU/L (nl, 0.5‐ 5.0)
What is the most likely endocrine diagnosis?
A. Primary hypothyroidism
B. Secondary hypothyroidism
C. Euthyroid sick syndrome
D. Thyroid hormone resistance
E. Subacute thyroiditis from HIV infection
C. Euthyroid sick syndrome (decr a little, TSH normal)
```
NOT
A. ↑TSH
B. ↓TSH
D. ↓feedback-->↑TSH-->↑T3 T4
E. Gland ↑T3,4-->↓TSH-->↓T3,4--> ↑TSH
```
75
Serum hormone concentrations in Euthyroid Sick Syndrome?
↓T3 & ↑rT3
↓T3 when sick due to metabolic rate (dont want thryoid hormone when ill) so TSH normal/high but low T3 T4)
76
T4-->T3 by which enzyme?
5'-deiodinase
77
A 33 y/o male takes L‐thyroxine 1 μg orally each day. He asks how the thyroxine works on a cellular levels. Which is the best explanation?
A. It binds to membrane surface receptor and actives protein synthesis
B. It binds to membrane surface receptor and activates a secondary messenger.
C. It binds to a cytoplasmic receptor, and the hormone‐receptor complex diffuses into the nucleus to affect transcription.
D. It has a direct effect on the hypothalamic nuclei affecting metabolism.
C. -->protein syn (stable and easy to replace/maintain levels)
NOT
B. protein/peptide H (hard to replace, fast (insulin)
78
A 15 y/o female has a BMI of 16 and is suspected of having anorexia nervosa. Thyroid function tests show a TSH in normal range but an elevated rT3. Which is the most accurate statement?
A. Reverse T3 has little biological effect
B. The patient has thyroiditis
C. The patient has hypothyroidism
D. Free T3 would be the next step to evaluate thyroid function
A. rT3 is inactive TH
79
The synthesis of posterior pituitary peptide hormones, ADH and oxytocin, are stored as prohormones but are made in the ____________.
pre-->propressophysin → ADH
pre-->prooxyphysin → oxytocin
hypothalamus
80
Oxytocin functions in milk letdown and uterine contractions (post/partum bleeding) while ADH functions to...
- maintain normal osmolality of body fluids and normal blood volume
- Released in response to increased serum osmolality
- Works on principle cells of the distal tubule to increase water resorption
- Induces contraction of vascular smooth muscle to protect against severe volume depletion
81
ADH:
Which receptor does ADH work through to increase water permeability of the principal cells?
Which receptor does ADH work through to induce contraction of vascular smooth muscle?
V2R (adenylyl cyclase coupling)
V1R (phospholipase C)
82
ADH increases expression of _________ on the luminal side of principal cells
• Water flow from the lumen to the renal interstitium is increased
• ADH decreases urine flow and urine osmolality ↑
• In the absence of ADH urine flow increases and osmolality ↓
aquaporin 2
83
What are two examples of stimulating factors of ADH secretion?
1) Increased blood osmolarity, ex. Dehydration
2) Hypovolemia, ex. Hemorrhage‐ a 10% decrease in ECF causes a decrease in arterial blood pressure and signals ADH secretion
(Ethanol inhib ADH)
84
What are the two pathways involved in ADH secretion?
- Osmoreceptors in the brain
| - Baroreceptors in the periphery
85
What is the pathophysiology of ADH in neurogenic diabetes insipidus?
- (central)‐failure of posterior pituitary to secrete ADH (unreg ADH)
- Circulating ADH low (gene muts, destruction of hypothal or post. pit)
- permeability of collecting ducts is decreased
- Dilute urine/ concentrated serum
- Water restriction has NO effect
86
What is the pathophysiology of ADH in nephrogenic diabetes insipidus?
- secondary (unresponsiveness to ADH)
- Posterior pituitary normal but defect in TARGET tissue (V2 receptor or aquaporin 2)
- ADH levels are high
- Dilute urine/ concentrated serum
- Lithium (interfere with V2 receptors)
87
Diabetes Insipidus (DI):
- Distinguish if polyuria is due to an increase in an osmotic agent (i.e. glucose) or due to renal disease
- Diagnosis of DI confirmed by what?
Dehydration stimulus followed by the inability to concentrate urine
88
- Normal/high plasma osmolality
- Low urine osmolality
- Low plasma ADH
- No change in urine osmolality after water restriction
- No change in plasma ADH after water deprivation
- Incr in urine osmolality after ADH admin
Neurogenic DI
89
- Normal/high plasma osmolality
- Low urine osmolality
- Normal to high plasma ADH
- No change in urine osmolality after water restriction
- Incr in plasma ADH after water deprivation
- No change in urine osmolality after ADH admin
Nephrogenic DI
90
-Excess ADH ex. Tumor secretion of ADH (ex. of preneoplastic syndrome in lung), trauma, anesthesia
-ADH secretion not linked to normal regulatory mechanisms
-Hyponatremic
• Primary‐ increased water resorption (high urine osmolarity, fix w/ H20 restriction)
• Secondary‐ atrial natriuretic peptide (ANP) triggered by increased blood volume
-Low serum osmolality
-Urine osmolality is inappropriately high
-Condition corrected upon water restriction
Syndrome of inappropriate ADH (SIADH) (too much ADH)
91
A 27‐year‐old white male presents with polydipsia (excessive thirst) and polyuria (excessive urination) with dilute urine
Labs:
-Low urine specific gravity
-Low urine osmolarity
-Elevated serum osmolarity
-Hypernatremia
-Upon water deprivation test, still cant concentrate urine
-Imaging shows lesion in the hypothalamus
Treatment?
Neurogenic DI
Treatment: replace ADH
ADH deficiency due to damage to hypothalamus
92
```
A 72‐year‐old male smoker presents with headache, weakness, fatigue, and decreased urinary output. He was recently diagnosed with oat cell carcinoma.
Labs:
-Hyponatremia
-Decreased serum osmolality
-Urine osmolarity increased
-Hypernatriuria
-Hypouricemia
```
SIADH
93
What is the correlation between the physiologic response of catecholamines to symptoms of excess catecholamine production in the case of a pheochromocytoma.
Epinephrine stimulates B2 receptors (highest affinity) to increase hepatic glucose output & decrease contraction of blood vessels
Also stimulates:
- B1 on heart-->incr CO, HR
- a1-->incr vascular SM contraction, incr BP, cold hands/feet
94
What is the appropriate biochemical assay in the case of suspected:
Adrenal insufficiency
Rapid ACTH stimulation test
95
TQ
What is the appropriate biochemical assay in the case of suspected:
Cushing’s syndrome
1. Suspect cushings
2. exclude exog steroid use
3. Perform 1 mg overnight DST OR late night salivary cortisol OR 24h urine free cortisol
4. Confirm postitive test with 1-2 additional studies
5. Cushing syn confirmed, proceed to cause
96
What is the appropriate biochemical assay in the case of suspected:
Primary hyperaldosteronism
(Both screening and confirmatory tests)
Screening: ratio of aldosterone to plasma renin activity
Confirmatory: Infusion of normal saline and then assay aldosterone (suppression test....fluids should decr aldos)
97
The synthesis of catecholamines by the adrenal medulla is under control of what?
CRH‐ACTH‐cortisol axis
- ACTH stimulates synthesis of DOPA
- Cortisol increases PNMT enzyme-->epi
(Release is triggered by CNS control)

98
Norepinephrine and Epinephrine are synthesized in different cellular compartments. Where are each synthesized?
NE: Chromaffin granule
Epi: Cytosol (PMNT enzyme)
99
What are the two enzymes used for the degradation of catecholamines?
Excreted in urine (24 hr sample)
COMT: catecholamine‐O‐methyltransferase
MAO: monoamine oxidase
100
What are some physiologic responses of the stress response?
Hint: Goal is to increase nutrient supply to muscle and O2/glucose-->brain
- Incr HR (CO)
- Vasoconstriction of veins (Incr venous return)
- Vasodilation of muscle arterioles (incr blood flow to skeletal m.)
- Vasoconstrict splanchnic arterioles (decr blood flow to GI)
- Dilation of bronchioles (incr O2)
- Decr motility of GI (E to other places)
- Incr lipolysis, gluconeogenesis, glycogenolysis, decr insulin and incr glucagon
101
-Produces excess catecholamines (norepi)
-Symptoms sporadic/pulsatile
-TRIAD: Headaches, sweating, Palpitations
Also:
-HTN
-Orthostatic hypotension (volume depletion)
-Anxiety
-Chest pain
-Flushing
Pheochromocytoma
| tumor of chromaffin tissue
102
- HPI: A 48 y/o women visits her physician complaining of what she calls “panic attacks”. She has experienced a racing heart, headaches, cold hands and feet, visual disturbances, nausea, and vomiting.
- PE: BP 230/125, orthostatic hypotension
- Labs: 24 hour urine sample shows elevated metanephrine, normetanephrine, and VMA
- Imaging: A 3.5 cm mass was found in the left adrenal
```
Which of the following agents should be administered first to control Lily’s blood pressure prior to surgery?
A. An α1‐adrenergic agonist
B. A β‐adrenergic agonist
C. An α1‐adrenergic antagonist
D. A
```
C. (decr vasoconstriction)..also GIVE FLUIDS if volume depleted
NOT
D. If volume depleted and decr HR then ischemic necrosis risk
103
- regulates salt and water retention)
- functions in salt and water homeostasis
- also effects potassium
Aldosterone (mineralcorticoid)
104
- increases plasma glucose
- released in response to stress
- influences glucose utilization, immune and inflammatory homeostasis (anti-inflam, immunosupp)
Cortisol (glucocorticoid)
| incr blood glucose and decr insulin receptor sensitivity
105
What is DHEA?
An androgen
106
Congenital adrenal hyperplasia w/ a deficiency in 17‐α‐hydroxylase leads to an incr/decr in the level of the following...
- mineralocorticoids (aldosterone)
- glucocorticoids (cortisol)
- Androgens (sex hormones)
- BP
- Potassium
```
Incr mineralocorticoids (HTN)
Decr glucocorticoids (cortisol)
Decr androgens (feminizing)
Incr BP
Decr postassium
```
107
```
Congenital adrenal hyperplasia w/ a deficiency in 21‐hydroxylase leads to an incr/decr in the level of the following...
-mineralocorticoids (aldosterone)
-glucocorticoids (cortisol)
-Androgens (sex hormones)
-BP
-Potassium
Labs?
```
```
Decr mineralocorticoids (salt wasting)
Decr glucocorticoids (cortisol)
Incr androgens (virilizing)
Decr BP
Incr postassium
Incr renin
```
108
```
Congenital adrenal hyperplasia w/ a deficiency in 11β‐hydroxylase leads to an incr/decr in the level of the following...
-mineralocorticoids (aldosterone)
-glucocorticoids (cortisol)
-Androgens (sex hormones)
-BP
-Potassium
Labs?
```
```
Moderate mineralcorticoid (decr aldoes but incr in DOC-->HTN)
Decr glucocorticoids (cortisol)
Incr androgens (virilizing)
Incr BP
Decr postassium
Decr renin
```
109
-Mutation in CYP21A2
-Block in 11‐deoxycorticosterone synthesis from progesterone
-May lead to total loss of glucocorticoid and mineralocorticoid activity-->
-Salt‐wasting
-Hyponatremia + hyperkalemia (decr mineralcorticoids)
-Hypotension (decr cortisol & aldosterone)
-Cardiovascular collapse and possibly death
-Virilization‐ recognizable in females at birth but more difficult in males

21‐Hydroxylase Deficiency
110
- Mutation in the CYP11B1 gene that results in a loss of activity and a block in the conversion of 11‐deoxycortisol to cortisol
- Loss of negative feedback inhib and incr ACTH-->incr androgens excess is observed
- Mineralcorticoid activity due to deoxycorticosterone (DOC)... incr secretion may be responsible for hypertension
- Cortisol is absent (hypogly)
11β‐Hydroxylase Deficiency
111
-Autosomal-recessive mutation of CYP17 gene
-Impaired sex steroid and cortisol biosynthesis
-Excess intermediary steroids w/
mineralocorticoid activity-->HTN + hypokalemia
-No androgen activity (females fail to develop secondary sexual
characteristics & males develop ambiguous external genitalia)
17α‐Hydroxylase Deficiency
112
A full‐term infant is delivered by an uncomplicated vaginal delivery. An endocrinologist is consulted because the pediatrician is unable to discern if the child is male or female. Laboratory tests showed a decr blood glucose of 70 mg/dL, low serum cortisol levels, elevated serum ACTH, and elevated 17‐ ketosteroids. The child was further determined have an XX genotype.
```
Predict how the following serum values will be altered in this case compared to normal.
Aldosterone
Kt
Na
Renin
```
21‐Hydroxylase Deficiency
Decr aldosterone
Incr K
Decr Na
Incr Renin (low blood volume)
113
A 17‐year‐old female is referred to an endocrinologist owing to lack of menses and absence of pubic hair, axillary hair, and breast development.
-She also complains of frequent headaches and ringing in her ears (due to hypertension)
-BP 160/105
Labs show:
-hypokalemia
-hypernatremia
-metabolic alkalosis
-suppressed renin
-diminished 17‐ ketosteroids and serum estrogen
-increased progesterone, pregnenolone, 11‐deoxycorticosterone, and corticosterone
```
The most likely enzyme deficiency is:
A. 17α‐hydroxylase
B. 21‐hydroxylase
C. 11β‐hydroxylase
D. Aromatase
```
A. 17α‐hydroxylase
114
What are the 3 causes of Cushings syndrome?
- ACTH‐dependent (adenoma-->Incr ACTH)
- ACTH‐independent (adenoma of adrenal gland)
- Factitious (high dose glucocorticoids in ex: IBD)
115
CC: Weakness and fatigue.
PE: Corti Solemia is a 47 y/o man with worsening weakness and fatigue. It was noted the patient had red cheeks and reddish‐purple striae on the lower abdomen and thighs. There was also an abnormal distribution of body fat with central adiposity and thin extremities. The patient also had thin skin, numerous bruises, and muscle weakness. Corti’s blood pressure was 165/105 and his fasting glucose was 160 mg/dL (nl, 70‐ 110).
Suspect Cushings so...
- Urine free cortisol levels were 300 μg (nl, 20‐90)
- Overnight dexamethasone suppression of cortisol test, 8 am plasma cortisol levels were 25 μg/dL (nl, 20)
- Imaging: adrenal mass on L adrenal gland
```
The results from Corti are most consistent with an overproduction of:
A. CRH from the hypothalamus
B. ACTH from an anterior pituitary tumor
C. ACTH from a posterior pituitary tumor
D. Cortisol from the adrenal cortex
E. Cortisol from an adrenal tumor
```
E. Cortisol from an adrenal tumor (this is why dexamethazone didn't effect levels...not under physiologic control)
NOT A b/c that would -->Incr ACTH
116
Pt w/ cushings has increased central obesity, muscle wasting, and striae. What are the biological effects of cortisol that are responsible for each of these physical findings? May also see moon face and hair growth, stunted growth
What will you see on bone scan?
Why HTN/high BP?
cortisol-->
Incr gluconeogenesis
Incr protein breakdown
Decr collagen (stria and bruising)
Osteoporosis (cortisol-->decr bone mass...so do glucocorticoids)
Cortisol maintains vascular responsiveness to catecholamines (if ↓ cor
117
Some cases of marked hypercortisolemia are associated with a hypokalemic alkalosis. What is the physiologic basis for the hypokalemia in these cases?
A. Oversaturation of 11β‐hydroxysteroid‐dehydrogenase (11β‐HSD2 enzyme)
B. Overproduction of aldosterone in the same tumor
C. Upregulation of mineralocorticoid receptors in renal epithelial cells
D. Overproduction of aldosterone in response to ACTH
A. enzyme actives cortisol
NOT
C. no need if already stim
D. ACTH doesn't regulate aldosterone!!!! RAAS does
118
TQ
T/F
ACTH does NOT regulate aldosterone. RAAS does
TRUE
119
Cushings pt had his left adrenal gland removed and was subsequently placed on exogenous glucocorticoids. What is the rationale for replacement of glucocorticoids at this time?
A. The pituitary corticotrophs have atrophied over the dz course
B. The rt adrenal gland will not produce adequate cortisol levels
C. Pt has adapted to higher than normal levels of cortisol and needs additional cortisol
D. Cortisol helps recovery after surgery
A. The pituitary corticotrophs have atrophied over the dz course (dont need to make ACTH...cells need time to incr ACTH prod)
NOT
B. able to produce cortisol
D. true but irrelevant
120
What are the main causes of primary adrenal insufficiency (Addison's dz)?
-Autoimmune (no cortex)...#1USA
-Metastatic disease
-Adrenalectomy
-Infectious adrenalitis:
Tuberculosis (#1 worldwide)
Disseminated fungal infections
HIV
121
-HPI: A 40‐year‐old female is admitted to the hospital for evaluation of increasing weakness and intermittent episodes of dizziness, nausea, and vomiting related to stress and exercise.
-PE: She presents with tachycardia (HR 110) and hypotension (BP 90/65). She has pigmentation of her buccal mucosa and on the palms of her hands (looks tan)
-Labs:
Low Na+ 135 mEq/L (nl, 136‐145)
High K+ 5.2 mEq/L (nl, 3.5‐ 5.0)
Cl‐ 100 mEq/L (nl, 95‐105)
Low random glucose 60 mg/dL (nl, 65‐120)
Low random cortisol 3 mg/dL (nl, 5‐25 mg/dL)
A rapid ACTH stimulation test failed to raise cortisol levels above baseline
```
Her deficiency is in the:
A. Hypothalamus
B. Pituitary gland
C. Adrenal gland
D. Tissue glucocorticoid receptor
```
C. Adrenal gland
122
```
In primary adrenal insufficiency, absence of which hormone accounts for hyponatremia, hyperkalemia, and hypotension?
A. Cortisol
B. Aldosterone
C. ACTH
D. Renin
```
What about hypoglycemia?
B. Aldosterone (hyperkalemia)
Hypogly due to loss of cortisol
123
The presentation of primary adrenal insufficiency is distinct from secondary adrenal insufficiency in that:
A. Secondary adrenal insuff usually presents with hyperpigmentation
B. Secondary adrenal insuff results in loss of aldosterone secretion
C. Primary adrenal insuff usually presents with hyperpigmentation
D. Renin levels are suppressed in primary adrenal insufficiency in comparison to secondary
C! Incr ACTH cross reacts with melanocytes
NOT
B b/c aldosterone is normal
124
Cross reaction of ACTH and melanocytes:
- MC2R receptors are on the surface of the adrenal gland and ACTH binds these receptors (ACTH also incr w/ incr POMC)
- At high levels, ACTH can cross‐react with _____ receptors on melanocytes, thereby increasing pigmentation
MC1R
125
-characterized by excessive production of aldosterone
– Bilateral hyperplasia of the zona glomerulosa (idiopathic hyperaldosteronism [IHA])
– Solitary aldosterone‐producing adenoma
– Adrenal carcinoma
– Glucocorticoid‐remediable aldosteronism
Tx may include removal of adrenal gland
Primary Hyperaldosteronism
126
HTN, hypokalemia, metabolic alkalosis, hypomagnesmia w/ muscle weakness
Primary hyperaldosteronism
127
In primary hyperaldosteronism, what factors keep sodium levels from being highly elevated?
What causes acid-base status to change?
Na escape phenomenon (even though K out)
Metabolic alkalosis due to loss of K=loss of H+-->incr pH
128
- Progressive wt gain in abdomen
- Face rounded
- Stria
- Hyperglycemia
- Bruising
- Muscle wasting
- Osteoporosis
- HTN
- High ACTH in urine
Dx? How?
What about androgen levels? Potassium?
Tx?
Cushing disease (excess ACTH) due to adenoma of pituitary
Diagnosed via 24 h free urine cortisol or dexamethasone suppression test
Incr ACTH-->incr androgen-->amenorrhea + hair growth
Potassium normal!!! Aldosterone ok...RAAS regulated aldosterone
129
Treated cushing's pt presents with nausea and weakness. Pt stopped taking prescribed medication. What is the cause of the symptoms?
Decr cortisol-->secondary insuff
Usually presents with a stressful event when your body needs cortisol
130
John is a 51 year old man who comes to the emergency room with severe abdominal pain and a fever. He has a history of inflammatory bowel disease for the last 15 years for which he took high dose prednisone (60 mg/day) for more than 5 years. When he saw a GI specialist last year, he was started on a new drug for his inflammatory bowel disease that was quite helpful. As a result, the prednisone was gradually tapered and then stopped 3 months ago. 12 hours ago he began having severe abdominal pain and felt dizzy. His blood pressure is 80/40 and his pulse is 120 bpm. His temperature is 101oF, and his abdomen is extremely tender.
Dx and why now?
What tests are ordered?
Secondary adrenal insufficiency due to prednisone inhib pituitary axis-->atrophy of pituitary (cant make cortisol)
Pt has fever=infection (stress)
Order a ACTH stimulation test
131
Why do patients with secondary adrenal insuff have hyponatremia?
Cortisol deficiency-->
Low BP, Incr CRH-->
Incr ADH-->
H20 reab
132
Pt presents w/...dx and tx?
- Hypoglycemia
- Anorexia, weight loss, nausea, vomiting
- Weakness
- Hypotension
- Hyperkalemia
- Metabolic acidosis
- Decreased pubic and axillary hair in females
- Hyperpigmentation
High ACTH levels
Dx: Addison disease (primary adrenocortical insufficiency)
Tx: Replacement of glucocorticoids and mineralocorticoids
note: Decr cortisol-->Incr ACTH
133
Pt presents w/...dx and tx?
- Hyperglycemia
- Muscle wasting
- Central obesity
- Round face, supraclavicular fat
- Osteoporosis
- Striae
- Virilization and menstrual disorders in females
- Hypertension
Decreased ACTH
Dx: Cushing syndrome (e.g., primary adrenal hyperplasia)
Tx: Ketoconazole, Metyrapone
note: Incr cortisol-->decr ACTH
134
Pt presents w/...dx and tx?
- Hyperglycemia
- Muscle wasting
- Central obesity
- Round face, supraclavicular fat
- Osteoporosis
- Striae
- Virilization and menstrual disorders in females
- Hypertension
Increased ACTH
Dx: Cushing disease (excess ACTH)
Tx: surgical removal of ACTH‐secreting tumor
135
- Hypertension
- Hypokalemia
- Metabolic alkalosis
- Decreased renin levels
No change in ACTH
Dx: Conn syndrome (aldosterone‐secreting tumor)
Tx: Aldosterone antagonist (e.g., spironolactone), Surgery
136
- Virilization in females
- Early acceleration of linear growth
- Early appearance of pubic and axillary hair
- Symptoms of deficiency of glucocorticoids and mineralocorticoids
Increased ACTH
Dx: 21β‐hydroxylase Deficiency
Tx: Replacement of glucocorticoids and mineralocorticoids
note: decr cortisol-->incr ACTH
137
- Lack of pubic and axillary hair in females
- Symptoms of deficiency of glucocorticoids
- Symptoms of excess mineralocorticoids
Incr ACTH
Dx: 17α‐hydroxylase Deficiency
Tx: Replacement of glucocorticoids Aldosterone antagonist (spironolactone)
note: decr cortisol-->incr ACTH
138
TQ What effect does estradiol (ovaries) have on the anterior pituitary?
POSITIVE FEEDBACK incr LH
139
What are the effects of untreated primary hyperparathyroidism on the bone and kidneys?
x
140
- Twitching
- Muscle cramps
- Tingling
- Numbness
Hypocalemia
| <8.5
141
- Constipation
- Polyuria
- Polydispia
- Lethargy
- Coma
- Death
Hypercalcemia
| >10.6
142
TQ
| What are the 4 functions of PTH?
1. Mediate Ca resorption (bone resorption)-->incr Ca in blood
2. Increase Ca resportion at kidney level
3. Decr phosphate reabsorption (Ca and phosphate opposite)
4. Incr conversion of 25-hydroxy vit D to 1-25dihyroxy vit D (active form)...if too high-->hypercalemia
143
What are the 3 functions of
| 1-25dihyroxy vit D ?
- Incr reab in gut
- Also helps PTH reabsoprtion and bone mineralization
- Incr Ca resoprtion and phosphate absorption in the kidney
Intestine, bone, kidney all involved!
144
What effect does high 1-25-dihydroxy vit D have on the enzyme 1 alpha hydroxylase?
Inhibits it! (inhibits formation of itself!
145
What is the only condition in which you see high PTH and high Ca in the blood?
Primary hyperparathyroidism
146
Hypercalcemia of malignancy has 2 forms. What are they and what are the mechanisms?
-Tumors secrete peptide similar to PTH (PTHRP) w/ similar actions-->high calcium and decr PTH from parathyroid
Bone lesions have high calcium (inflammatory-->stimulate RANK/RANKL)
147
- Thiazide diuretics
- Milk-alkali syn
- Immobilization (immobile pts)
- ACUTE renal failure
- Granulomatous dz
- Vit D intox
- Vit A intox
- Hyperthyroidism
-->PTH-independent hypercalcemia
148
Major causes of hypocalcemia? (3)
- Vit D deficiency (lose 1-25 dihydoxy)
- Hypoparathyroidism (loss of PTH)
- CHRONIC renal failure (affects 1-25 vit D)
149
- Extreme pain in right thigh radiating into groin starting after two sets of tennis on a hot July day. “Worst pain of his life”. Urine at the time was bright red. Recent onset of constipation.
- Imaging: Contrast CT=Two small stones identified in his right ureter
- Follow up: He was prescribed narcotics and sent home. That evening he passed two kidney stones. On a fu visit the next day, labs=
- High serum Ca
- High intact PTH
- Low serum phosphate
- High ALP
- High Ca excretion
- Normal albumin
- Urinary stone=calcium oxalate
```
Pt has unregulated secretion of PTH due to an adenoma of the parathyroid gland. Under physiologic control, which form of calcium stimulates PTH secretion?
A. Total calcium
B. Ionized calcium
C. Protein‐bound calcium
D. Anion‐complexed calcium
```
Why incr ALP?
B. Ionized calcium
Incr ALP due to bone formation-->
However, anytime bone formation there is bone resorption! They are linked
150
TQ
In a pt with primary hyperparathyroidism due to adenoma of parathyroid, what would we conclude re: serum calcium levels if his albumin was elevated above the normal range?
Incr albumin may lead to normal calcium levels because it binds calcium!
151
How will the levels of ionized calcium change upon development of alkalemia?
A. Increase
B. Decrease
C. Stay the same
B. Decrease
alkalemia-->decr ionized Ca
Incr pH-->decrease H+-->
Albumin releases H+-->
Incr binding Ca binding sites-->
Decr Ca
If acidotic:
Incr H+-->
Decr Ca binding-->
Incr Ca
Hyperventilating-->
Incr pH-->Decr H+-->
Decr calcium
(respiratory alkalosis)
152
```
In patients with mild hypercalcemia, observation may be appropriate for treatment. Observation should include monitoring blood calcium and creatinine every 6 months and yearly bone densitometry. On which cell type do the PTH receptors reside?
A. Osteoblast cells
B. Osteoclast cells
C. Osteocyte cells
D. Chrondrocytes
```
A. Osteoblast cells
Release factors for osteoclast precursors
153
What is the outcome of increased PTH secretion on the bone homeostasis?
A. Net bone deposition
B. Net bone resorption
C. No net change
B. Net bone resorption
154
```
What is the impact of elevated PTH levels on the
kidney?
A. Increased production of 1,25 (OH)2 D3
B. Decreased production of 1,25 (OH)2 D3
C. Increased phosphate retention
D. Increased calcium excretion
```
A. Increased production of 1,25 (OH)2 D3
NOT
C: Incr phosphate excretion!
D: Increases calcium retention!
155
What is the significance of increased phosphate excretion on serum calcium levels?
Calcification may occur...
Incr P + Incr Ca (ionizied)-->
Complex of P-Ca-->
Calcification of soft tissues
156
Why do we see hypercalciuria in pts with primary hyperparathyroidism? (ex: calcium stones)
Pt presented with kidney stones upon dehydration. What is the mechanism responsible for this event?
A. Increase in ADH secretion and concentration of urine
B. Increase in ADH secretion and water retention
C. Decrease in ADH secretion and increased urinary flow
D. Decrease in ADH secretion and worsening of hypercalcemia
Ca is being lost in the urine
A. Increase in ADH secretion and concentration of urine
157
-CC: Hip pain
-HPI: A 30‐year‐old white male without a significant past medical history is admitted to the orthopedic department because he sustained a right femoral neck fracture when he fell from a small stool; the type and magnitude of the fracture are not compatible with the patient’s age and impact. The patient further reports increasing leg weakness and persistent lower back pain.
-PE: Vitals: Temp = 100.0, RR = 18, Pulse = 111, & BP = 150/95. He has right hip and leg tenderness to palpation; there is pain when pressure is applied to both tibias.
-Labs:
Low vit D (
B. Vitamin D deficiency
A. Osteomalacia (adults...secondary cause of osteoporosis w/ T score)
158
-A 62 y/o male presents with nausea, vomiting, fatigue and generalized weakness. He has a past medical history of long standing type 2 diabetes, hypertension, and hyperlipidemia. He has nephropathy and declining renal function for the last 3 years from his diabetes. Upon further questioning, his urine output has decreased for the last 2 weeks.
-On physical exam, Temp = 99.2, pulse = 95, RR = 20, and blood pressure = 180/110. He has pitting edema in both legs up to his sacrum.
-Upon presentation, his serum Cr = 5.5 and BUN = 110
(renal failure)
Bone loss associated with renal failure occurs in part because:
A. The failing kidney is no longer capable of PTH production
B. Renal phosphate clearance decreases in renal failure
C. The failing kidney increases activation of vitamin D
D. Renal calcium clearance increases in renal failure
B. Renal phosphate clearance decreases in renal failure
NOT D
Ionized phosphate and calcium complex and then are excreted together in urine...probably see calcification
159
Renal osteodystropy (bone problems associated with renal failure) is characterized by:
A. A decrease in serum PTH levels
B. An increase in urinary phosphate levels
C. An increase in serum calcium levels
D. A decrease in 1α‐hydroxylase activity
D. A decrease in 1α‐hydroxylase activity (-->active vit D)
NOT
A: hypocal-->incr PTH (secondary hyperparathyroidism)
B: Incr PTH-->Incr phosphate but decr in kidney fx so cant excrete phosphate (decr GFR)
C. Decr 1-25 vit D
160
- CC: Muscle cramps and tingling of the lips.
- HPI: An 8 y/o girl presents with perioral parasthesias and severe muscle cramping of the upper & lower extremities. She is unable to walk or flex her arms.
- PMHx: Type 1 diabetes, Addison’s disease, and hypothyroidism (autoimmune dz clustering)
- FHx: she is adopted; her biologic brother has type 1 diabetes, celiac disease and hypothyroidism
- SHx: lives with mother, father, and brother; vaccinations up to date
- Muscle rigidity
- Decr calcium, decr PTH, incr Phosphorous
She has low serum calcium levels due to:
A. autoimmune destruction of her pancreas.
B. autoimmune destruction of her parathyroid glands.
C. inadequate calcium in her diet.
D. inappropriately low 25(OH) vitamin D level.
E. PTHresistance.
B. autoimmune destruction of her parathyroid glands
Clustering of autoimmune diseases!!
Decr PTH so replace with 1-25 vit D (no hydroxylase)...if normal PTH then tx with dietary 25 vit D
161
66 year old reports that she remained well after removal of the pituitary tumor (she had Cushing’s disease). She had her last period 14 years ago and has not taken estrogens because she was afraid they would cause her to gain weight – nevertheless, she did gain about 20 lbs, from 120 to 140 lbs. Her height is 5’0’’. She has not suffered from hot flashes. Her estimated dietary calcium intake is 250 mg/day (low). She exercises occasionally and takes no medications. She smokes 1 pack of cigarettes a day. Physical examination is normal, except for being moderately overweight. Spine x‐rays show no fractures. Bone density in the spine is 2.8 standard deviations below the mean for young normal. Jennifer’s lab values are as follows:
- Incr bone-specific alkaline phosphatase
- Incr urine n-telopeptides
- Normal Ca and Vit D
```
What is the most likely diagnosis in this case?
A. Osteomalacia
B. Osteopetrosis
C. Osteoporosis
D. Paget’s disease
E. Osteogenesis imperfecta
```
```
Which explanation directly accounts for the slightly elevated alkaline phosphatase level?
A. PTH levels are elevated
B. Bone resorption rates are increased
C. Dietary calcium intake is inadequate
D. Vitamin D levels are insufficient
```
Which factor is working in Jennifer’s favor in terms of disease prevention?
A. Dietary calcium intake B. Physical activity
C. Cushing’s disease
D. Menopause
E. Weight
C. Osteoporosis! (post-meno)
Normal to have normal Ca and Vit D levels
B. Bone resorption rates are increased
E. Weight
:) wt is good for bone density (pressure on bones decr loss)
:( low dietary ca + smoker
162
What is increase urine n-telopeptides indicative of?
Bone resportion/remodeling
163
TQ
| Estrogen effects of relative bone mass related to age
Bone loss around time of menopause-->sharper decr in bone mass than men
164
Risk factors for Osteoporosis?
```
Nonmodifiable:
Age
Race (Caucasian, Asian) Gender
Menopause
Build
Family history
```
```
Modifiable:
Calcium intake
Vitamin D intake
Estrogen deficiency
Sedentary lifestyle
Smoking
Alcohol excess
Caffeine excess
Medications
```
165
Tx of osteoporosis?
Antiresorptive: inhibit bone resorption (i.e. bisphosphonates)
Anabolic: increase bone formation (i.e. subcutaneous PTH injections...pulses osteoblasts & osteoclasts)
If combined=no gain in effect
166
A 68‐year‐old man complains of a 10‐year history of progressive pain in the shins, knees, and left arm. He also notes progressive hearing loss. Physical examination reveals tenderness above the left elbow, enlarged, bowed shins and warmth over both shins. Bone scan shows intense uptake in multiple locations of the skeleton (shown to the right). Skeletal x‐rays show enlargement with multiple focal lytic and sclerotic areas throughout the skeleton.
-Laboratory evaluation reveals:
Normal Serum calcium = 9.8 mg/dL (nl = 8.5‐10.5)
High Alkaline phosphatase = 966 U/L (nl = 25‐125)
Normal Serum PTH = 25 mg/dL (nl = 10‐65)
Dx?
Why pain? Why tenderness and warmth?
Paget's dz
normal Ca and PTH
osteoblasts-->incr ALP
Pain due to incr act of osteoblasts
Incr bones-->hearing loss but bones are weak b/c not layed down in lamellar formation
Incr bone-->incr blood flow/circulation/vascularity-->warmth
167
Origin of defect in pagets?
Osteoblasts making ALP
168
```
Considering currently available therapeutics, which option should be utilized in the treatment of Paget's dz?
A. Calcium supplementation
B. Increase in urine output
C. Inhibition of bone formation
D. Inhibition of bone resorption
E. Inhibition of PTH secretion
```
D. Inhibition of bone resorption
(bisphosphonates=tx of choice)
(coupled to formation so formation also decr)
```
NOT
A: Ca normal
B: Bad for pt
C: DOESN'T EXIST :(
E. PTH and Ca normal
```
169
A 65 y/o postmenopausal female obtains a screening DEXA scan. Her T score is ‐2.8 at the right femoral neck. Other health problems include hypertension, hyperlipidemia and obesity. There is no history of fractures and the patient is a nonsmoker. The patient is a social drinker and her calcium intake is about 750 mg/day. A physical exam showed her BP = 135/80 and BMI = 32. No kyphosis was evident. Laboratory values showed:
- Decr 25 vit D
- Normal Ca, phosphorus, PTH, ALP, and creatine
Before giving bisphosphonates, what condition is treated first?
Osteoporosis (T score) w/ vit D def
Tx with vit D supp to minimize risk of hypocalcemia!
If give bisphosphonates first-->inhibit bone resorption-->decr Ca
If vit D low, then cant take up Ca from diet!
170
Secondary causes of osteoporosis?
```
– Vitamin D deficiency
– Increased PTH
– Renal failure
– Glucocorticoid excess
– Hypogonadism (post-meno)
– Increased thyroid hormone
– Idiopathic hypercalciuria
```
171
TQ
Give dx:
A. High PTH and Ca?
B. High Ca, Low PTH?
C. Low Ca, high PTH?
D. Low Ca, VERY high PTH?
A. Primary hyperparathyroidism
B. Metastatic bone dz
C. Vit D def
D. Kidney failure
