Physio Flashcards
What effect does GLP-1 (incretin) have on insulin release?
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
TQ
What are the causes of elevated blood glucose in type 2 DM? (3 due to obesity)
- 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
What is the pathophysiology of type 1 DM, both immunologic and metabolic?
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)
- 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
Type 1 DM (ketoacidosis)
Tx: IV fluids–>insulin–>decr K so electrolyte replacement
- Late onset
- Genetic (fam hx)
- Obese
- Hyperglycemia
- Hyperlipidemia
- A1c 8.4% (>6.5%)
Type 2 DM
The following hormones are released by which endocrine gland? TRH CRH GnRH GHRH Somatostatin Dopamine
Hypothalamus
The following hormones are released by which endocrine gland? TSH FSH LH ACTH GH Prolactin
Anterior pituitary
The following hormones are released by which endocrine gland?
Oxytocin
ADH
Posterior pituitary
The following hormones are released by which endocrine gland?
T3, T4
Calcitonin
Thyroid
The following hormones are released by which endocrine gland?
PTH
Parathyroid
The following hormones are released by which endocrine gland?
Inuslin
Glucagon
Pancreas
The following hormones are released by which endocrine gland?
Norepi
Epi
Adrenal medulla
The following hormones are released by which endocrine gland?
Renin
1,25-dihydroxycholecaliferol
Kidney
The following hormones are released by which endocrine gland?
Cortisol
Aldosterone
Adrenal androgens
Adrenal cortex
The following hormones are released by which endocrine gland?
Testosterone
Testes
The following hormones are released by which endocrine gland?
Estradiol
Progesterone
Ovaries AND
Corpus luteum
What is insulin’s structure?
What is the significance of C peptide as a diagnostic value?
Insulin is a peptide hormone and therefore requires 2 cleavages (preprohormone–>prohormone–>hormone)
This takes longer to synthesize.
Anytime C peptide=insulin release
What is the effect of insulin on glucose uptake and carb metabolism in muscle, liver, brain, and adipose tissue?
- 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
What is the effect of insulin on fat and protein metabolism?
Low insulin–>decrease breakdown
High insulin–>increase formation
What is the effect of insulin on serum potassium?
Majority of potassium excretion occurs in kidney is determined on aldosterone-renin-angiotensin pathway.
Insulin promotes movement of potassium into the intracellular space
What is the relationship between ketosis to insulin-deficiency?
What is ketoacidosis?
Insulin deficiency--> Incr lipolysis--> Incr FFA to liver--> Incr ketogenesis--> Increase ketoacidemia--> Incr acidosis
Also: Hyperglycemia--> Osmotic diuersis--> Decr renal fx--> Acidosis
What are the effects of glucagon on blood glucose concentrations?
Increases blood glucose
What promotes and suppresses both insulin and glucagon secretion?
Glucose stimulates insulin secretion by β-cells and suppresses glucagon from α-cells (via catecholamines)
What do patients with type 1 and type 2 DM have in common?
Nonenzymatic glycosylation of proteins
In type __ DM, there is reduced incretin effect, meaning that there is decreased release of GLP-1
2
Fasting glucose over ___ and 2 hr oral glucose (75 mg) tolerance test over ___=diabetes
126
200
What can be administered to raise blood glucose during hypoglycemic event?
glucagon
How does GH and gonadotropins influence insulin?
Block insulin so since high GH at night then high glucose in evenings (low insulin)
In a ketoacidotic diabetic pt, C peptide would likely be at ___ng/mL (normal 0.5-2.5)
0
no insulin
- 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
What are pregnant women susceptible to pituitary infarction?
Incr lactotropes»_space;
Incr size of anterior pituitary without corresponding incr in blood supply»_space;
Ischemia»_space; necrosis
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.
- 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
- 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)
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.
- Excess GH in adults
- Typically caused by pituitary adenoma
Acromegaly
Name a few factors which STIMULATE GH secretion.
- Fasting
- Stress
- Amino acids
- Hypoglycemia
Name a few factors which SUPPRESS GH secretion.
- Obesity
- High FFA
- Hyperglycemia
- Hypothyroidism
- IGF-1
Name a few factors which INHIBIT GH secretion.
- Acute and chronic illness
- GH receptor deficiency
- GHR antibodies
- IGF-1 receptor deficiency
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.
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.
How does GH affect insulin sensitivity?
GH impairs glucose tolerance, causing insulin resistance.
ß-cells of pancreas become exhausted»_space; insulin deficiency
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)
Summary of GH actions:
- Diabetogenic effect‐ causes insulin resistance
- glucose uptake
- blood glucose levels
- lipolysis
- blood insulin levels - 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 - 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
- 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 - Increased linear growth (through the actions of IGF‐I) Altered cartilage metabolism
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
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
What are the characteristics of Grave’s disease?
Hyperthyroid:
- Bulging eyes
- Thin
- Tremors
What are the characteristics of Hashimoto’s thyroiditis?
Hypothyroid:
- Edema
- Puffiness
- Wt gain
- Cold
- Goiter
- Skin changes
- Constipation
- HA
- Fatigue
- Anovulation
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
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
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:
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
T/F:
TRH is included in a thyroid test
FALSE
TRH is not in the serum! Acts on ant. pituitary and no systemic presence
What lab values do we see in hyperthyroid? (↑/↓)
TSH
T4
↓TSH
↑T4
- 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
- Exogenous thyroid hormone
- Gland atrophy
- Low thyroglobulin
Factitious thyrotoxicosis (hyperthyroid) -Tx too high (↓ thyroid fx) Ex: hasimotos
- “Hot nodule”
- Overprod of thyroid
- ↓TSH
- Gland atrophy around nodule
Toxic adenoma
- Granulomatous
- Viral
- Painful gland
- Transient cycles of hyperthyroid, euthyroid, hypo thyroid, euthyroid
Subacute thyroiditis
- Subacute lymphocytic
- Autoimmune
- non-tender gland
- Transient cycles of hyperthyroid, euthyroid, hypo thyroid, euthyroid
- Postpartum?
Silent thyroiditis
What is the one clinical exception to hyperthyroidism having ↓TSH?
pituitary overproduction of TSH
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
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
- 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
What is the most common disorder of hypothyroidism in iodine sufficient areas?
Hasimotos thyroiditis
Pt presents w/…
- Goiter
- skin change
- peripheral edema
- constipation
- headache
- fatigue
- anovulation
↑TSH and TRH
↓T3 and T4
Tx?
Replacement therapy with levothyroxine (T4)
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
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
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…
