Endocrinology (Clinical Review Q's)

Question 1

What would hyponatremia with an absence of edema indicate?

Answer 1

SIADH

low plasma sodium w no edema

Question 2

What might darkening skin/ hyperpigmentation indicate?

Answer 2

High levels of ACTH

Question 3

How can one shut down hormone production rapidly in hyperthyroid patients?

Answer 3

Clinically: very high iodide doses are used to rapidly shut down thyroid hormone production in hyperthyroid patients

Question 4

If you see a rise in hormones that are secreted by the pituitary what could this mean?

Answer 4

lung cell carcinoma- secretes hormones that would normally be secreted by pituitary and causes all sorts of endocrine problems

or pituitary tumor?

Question 5

Match disease to symptom…

postpartum hemorrhage/shock; results in massive pituitary cell death.

Answer 5

Trauma/Stress (endocrine pathology)

Sheehan’s Syndrome – postpartum hemorrhage/shock; results in massive pituitary cell death

Question 6

What is Kallman Syndrome?

Answer 6

Rare genetic disease (1:8000 men/1:40,000 women)
GnRH neurons fail to enter CNS
Characterized by reproductive failure and anosmia
Heritable: X-linked = Kal1, autosomal = Kal2

Question 7

What could a patient being treated with Lithium for bipolar disease experience? How/why?

Answer 7

DIABETES INSIPIDUS
Decreased renal responsiveness to AVP
Acquired: lithium treatment

also can have decreased renal responsiveness- most common reason in adults is acquired (lithium treatment prescribed for bipolar disease, enters through epithelial sodium channels but cant get out so accumulates inside cell and interferes w AVP abiity to traffic AQP2 channels) accumulation inside cell may either decrease AQP2 synthesis or increase lysosomal degradation of these channels

(Lithium can also inhibit NIS symporter in follicular epithelial cell)

Question 8

What will AVP levels be in a case of acquired diabetes insipidus?

Describe differential diagnosis.

Answer 8

-AVP levels typically normal bc thirst mech. can compenstate for changes in plasma osmolality

(differential diagnosis- alter plasma osmolality and see what happens through water restriction)

Question 9

What is the effect of treating someone with carbenoxolone?

What does carbimazole do?

Answer 9

Certain drugs (carbenoxolone) will inhibit 11B-HSD2 resulting in excess MR activation.

Carbenoxolone used to treat esophogeal inflammation – increases local cortisol

Carbimazole – inhibits thyroid peroxidase (TPO) -treatment for thyroid storm!

Question 10

What might happen if someone eats too much licorice? (real licorice/glycyrrhetinic acid)

Answer 10

Licorice (glycyrrhetinic acid) also inhibits 11B-HSD2 – excessive consumption can lead to increased sodium and water retention.

Question 11

Why might you target 11B-HSD1 for drug therapy for DM T2?

Answer 11

Local production of Cortisol by 11B-HSD1 potential pathogenic role in DM T2 – novel drug target

target enzyme bc idea is local prod. of cortisol esp in abdomen can contribute to obesity and type II Diabetes. so potential drug target

Question 12

What will a 21alpha hydroxylase deficiency lead to? Why?

What are some clinical indications?

Answer 12

Congenital Adrenal Hyperplasia (CAH)

21 alpha hydroxylase deficiency - results in excess DHEA, no mineralocorticoids or glucocorticoids

Most common cause of CAH

Clinical indications: virilization (masculinization) ambiguous genitalia at birth, sodium loss

No cortisol
No aldosterone/MR activity
Increased androgens

Clinical presentation:
Hypotension
Hyperkalemia
High plasma renin
Masculinization
High ACTH

Question 13

What are pheochromocytes?

What are pheochromocytomas?

Answer 13

chromaffin cells of adrenal medulla

Pheochromocytomas – tumors originating from chromaffin cells.

Pheochromocytomas: the 10% tumor

Question 14

What can vanillylmandelic acid levels be used to indicate clinically?

Answer 14

can be used to clinically detect tumors prod. excess EPI or NE.

Question 15

What could hypertension (no response to medication), headaches, and tachycardia indicate?

Diagnosis? What tests?
Treatment?

Answer 15

Pheochromocytomas – tumors originating from chromaffin cells.

Diagnosis: measurements of urinary metanephrines

Treatment: surgery, pre-surgery: alpha/beta blockers.

Question 16

What could opthalmopathy- edema behind eyes, and tachycardia indicate?

Answer 16

Graves disease -

Autoimmune – antibodies (Long-acting thyroid stimulator - LATS)
stimulate TSH receptor
- Elevated T4/T3
- Diffuse symmetrical goiters with hyperthyroid symptoms: tachycardia,
opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss,
nervousness, muscle wasting

Histology of thyroid gland from patient with Graves Disease. Note:
scant colloid, tall columnar activated follicular cells, and infiltration of
lymphocytes.

tachycardia- effects of thyroid hormone on heart med. those catecholamine effects
get opthalmopathy- edema behind eyes (defects in carbohydrate metabolism..buildup of polysaccharides in interstitial space which retains water… so these individual easy to spot bc looks like eyes bulging out of heads)

Question 17

Diffuse goiter with hypothyroid symptoms: lethargy, fatigue, hair loss, cold intolerance, brittle nails decreased appetite, weight gain.

Answer 17

Hashimotos Thyroiditis

Autoimmune destruction of thyroid follicles

Antibodies against TPO, TG

Question 18

Symptoms:

High fever
Tachycardia
Altered mental status
Severe nausea, vomiting, diarrhea
Severe circulatory collapse

What is diagnosis? How to treat?

Answer 18

CLINICAL DISORDERS – THYROID STORM

Emergency life threatening situation
Hyperthyroid coupled with severe acute illness
-normal hyperthyroid response … coupled w that massive up regulation of stress response, catecholamines v high…

can result in severe circulatory collapse bc all vessels dilate and body tries to perfuse all tissues at once, we don’t have enough blood to perfuse all tissues at once and circulatory system will eventually collapse

Treatment:
Propylthiouracil (PTU – only acute treatment)
Carbimazole (methimazole)
Beta blockers to restore normal heart function

PTU-treatment …will block thyroid peroxidase (TPO)…stop making thyroid hormone (some liver toxicity issues so not given long term)

carbimazole- given to inhibit TPO in hyperthyroid patients and give beta blockers.

Question 19

What is Kussmaul breathing?

What might this indicate in a patient? What type of diabetes?

Would labs show high or low PCO2?

Answer 19

deep rapid breathing

respiratory compenstaion in response to decreased bicarb and increased CO2

Low PCO2

Question 20

Why is the blood pressure low and the pulse rate high (T1DM)?

Answer 20

Dehydration – vomiting, osmotic diuresis results in low BP

Decreased baroreceptor firing (less stretch due to low blood flow) induces tachycardia.

Question 21

What is Sheehan’s Syndrome?

Answer 21

Sheehan’s Syndrome – postpartum hemorrhage/shock; results in massive pituitary cell death

Usually affects other pituitary cell types – loss of axillary and pubic hair

(progesterone will increase blood volume in preg. to anticipate possible hemorrhage… )

Question 22

What type of therapy for Crohn’s disease?

Answer 22

Glucocorticoid therapy

Question 23

Describe Euthyroid sick syndrome.

Answer 23

Hypothyroid symptoms with low T4/T3

Normal TSH and thyroid

Question 24

What is Laron Syndrome?

Answer 24

GH Deficiency
Dwarfism (children): related to GH

Laron Syndrome –
genetic defect in GH receptor – no production of IGF-I. Treatment with IGF-I can prevent dwarfism
Plasma GH levels are normal to high (lack of feedback).

Question 25

What is African Pygmy?

Answer 25

African Pygmy Partial defect in GH receptor – some IGF-I response. Plasma levels of GH normal – no pubertal increase in IGF-I.

Question 26

What would you see in adult GH deficiency? | What would this person be at risk for?

Answer 26

Caused by pituitary tumor/surgery or treatment (76%) Increased fat deposition, muscle wasting Reduced bone density, risk of fractures Higher LDL, Triglicerides

Question 27

What is Addison's disease?

Answer 27

Failure of adrenal to secrete glucocorticoids, mineralocorticoids, or both. Primary – failure at adrenal Addison’s Disease = autoimmune destruction of adrenals 70% of primary AI cases

Question 28

What is the Wolf-Chaikoff Effect?

Answer 28

WOLF-CHAIKOFF EFFECT: An intrathyroidal response that assures constancy of iodide storage in the face of changes in dietary iodide Increases in iodide intake decrease gland transport (solid line) and hormone synthesis (dashed line), and vice-versa Clinically: very high iodide doses are used to rapidly shut down thyroid hormone production in hyperthyroid patients this can be clinically useful in person w crisis… can shut down thyroid gland temporarily by overdosing w a lot of iodide.

Question 29

What is pertechnate? What is its significance? What is perchlorate? What is it used for?

Answer 29

Radioactive iodide (131I, 123I) and anions like pertechnetate (TcO4) can be transported by NIS Used to determine function of thyroid gland Organification defect - iodine cannot be incorporated into tyrosine. Test by blocking NIS with inhibitor (i.e. perchlorate)

Question 30

How will the following affect TBG levels? Hepatitis Steroids Estrogen Nephrotic syndrome

Answer 30

Estrogen, hepatitis increase TBG; nephrotic syndrome, steroids decrease TBG = no net change in “free” T4/T3.

Question 31

What is Grave's Disease?

Answer 31

Autoimmune – antibodies stimulate TSH receptor (Long Acting-Thyroid Stimulator – LATS) Elevated T4/T3 Diffuse symmetrical goiters with hyperthyroid symptoms: tachycardia, opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting

Question 32

What is Hashimotos Thyroiditis?

Answer 32

Autoimmune destruction of thyroid follicles Antibodies against TPO, TG Diffuse goiter with hypothyroid symptoms: lethargy, fatigue, hair loss, cold intolerance, brittle nails decreased appetite, weight gain now these antibodies are against TPO if you don't have TPO now you have organification defect, conjugation doesn't happen, cant convert iodide to iodine (TPO does all those things)

Question 33

If you found a bladder tumor and the patient also had hypercalemia, what conclusion might be appropriate?

Answer 33

Many tumors produce PTHrP (renal, bladder, lymphoma, head/neck) resulting in hypercalcemia more importantly than binding, this activates the same intracellular signaling pathways as PTH. so if you have a tumor secreting PTHrP you will have all same effects as if you had high levels of PTH.

Question 34

``` Deficiency linked to: Multiple Sclerosis Asthma Cardiovascular disease Type II Diabetes mellitus Colorectal/breast cancer Major Depressive Disorder (MDD) ``` What is deficient?

Answer 34

Vitamin D

Question 35

Reduced bone density – mainly trabecular bone Causes: genetic, menopause (low estrogen), glucocorticoid therapy/chronic stress, low dietary Ca2+ What is diagnosis and how is it treated?

Answer 35

Osteoporosis Treatment: estrogens, calcitonin, bisphosphonates (inhibit bone resorption), Vitamin D

Question 36

What could chronic renal failure lead to? Patient has hypercalcemia and kindey stones. (Primary and secondary causes)

Answer 36

Hyperparathyroidism Primary: hyperplasia, carcinoma of parathyroid gland Hypercalcemia, kidney stones Secondary: due to chronic renal failure Reduced Vitamin D leads to excess PTH synthesis

Question 37

What would the following indicate? Chvostek sign: twitching of facial muscles in response to tapping of facial nerve

Answer 37

Hypoparathyroidism Hypocalcemic tetany

Question 38

What would a Vitamin D deficiency in children and adults lead to?

Answer 38

Rickets (children)/Osteomalacia (adults) Unmineralized bone due to Vitamin D deficiency “bowing” of long bones (children) Decreased bone strength

Question 39

What is the following? Describe. Clinical signs: low Ca++, high phosphate, elevated PTH, short stature

Answer 39

Pseudohypoparathyroidism Congenital defect in G protein that associates with PTHR1 Clinical signs: low Ca++, high phosphate, elevated PTH, short stature Generalized resistance to PTH, TSH, LH, and FSH

Question 40

What would urinary hydroxyproline indicate?

Answer 40

Urinary hydroxyproline = enhanced bone resorption

Question 41

Name the following disease. How is it treated? Excessive localized regions of bone resorption and reactive sclerosis. Very high bone turnover Cause is unknown.

Answer 41

Paget disease CALCITONIN Therapeutic use: inhibits osteoclast reabsorption of and slows bone turnover (net effect = hypocalcemic action). “Escape” phenomenon – rapid downregulation of calcitonin receptors cause the antiosteoclastic actions of calcitonin to diminish within a few hours making this a less effective treatment option.

Question 42

What can PCBs (Polychlorinated biphenyl) cause? Why?

Answer 42

PCBs compete with thyroid hormone binding to its transport protein in the blood (TTR; TBG) Result: Increased breakdown of thyroid hormone Compensatory excessive production by thyroid gland Goiter (enlarged thyroid gland) Also causes cancer, immune function suppression (atrophied thymus), reduced sperm count, neurological deficits

Question 43

What chemical was later found to cause a 40% increase in cervical/vaginal cancers of daughters whose mothers were treated?

Answer 43

Diethylstilbestrol (DES) Non-steroidal synthetic estrogen Used in cattle feed Given to pregnant women from 1940-1970 to reduce complications Also used for prostate cancer treatment “DES daughters” = 40% increase in cervical/vaginal cancers

Question 44

Which chemical is an agonist for thyroid hormone receptor?

Answer 44

BPA Physiological Consequences: Estrogenic Obesogenic and diabetogenic (alters lipid homeostasis and pancreatic beta cell function) Neurological effects Antagonist for thyroid hormone receptor Reproductive and developmental effects (male and female) Cardiovascular disease – evidence for arrhythmias and atherosclerosis

Question 45

Change in body fat distribution – moon face, buffalo hump, abdominal obesity, thin skin, bruising Other symptoms? Disease?

Answer 45

Inhibition of intestinal calcium absorption – osteoporosis Hypertension – excess glucocorticoids activate MR Glucose intolerant – antagonism of insulin action Purple Striae – Fragile thin skin stretches over increased abdominal fat, vessels hemorrhage into striae **Also occurs with long-term glucocorticoid therapy “Cushing disease” – excessive cortisol secretion due to pituitary adenoma “Cushing syndrome” – all others

Question 46

How might you treat an insulin-producing tumor?

Answer 46

Somatostatin (SS14) – Inhibited by insulin Suppresses insulin release - used in clinic for management of insulin-producing tumors

Question 47

What is POMC a gene for?

Answer 47

ACTH – ADRENOCORTICOTROPIN HORMONE Precursor = POMC (pro-opiomelanocortin) (CRH prod. in PVN stimulates POMC in ant. pituitary to releas ACTH) also alphaMSH is cleaved from POMC which is an inhibotr of appetite and is stimulated by leptin

Question 48

Describe the factors Leptin stimulates and inhibits.

Answer 48

Stimulators Neuropeptide Y (both are neurons in hypothalamus) Agouti-Related Peptide (AGRP) **Leptin inhibits these causing decreased food intake Inhibitors αMSH – cleaved from POMC Cocaine-amphetamine regulated transcript (CART) **Leptin stimulates these decreasing food intak

Question 49

What would Elevated HbA1C: greater or equal to 48mMol/l (6.5%) indicate?

Answer 49

T2DM

Question 50

How does metformin treat T2DM? Sulonyureas? “Glyburide”, “Glipizide” Alpha-glucosidase inhibitors “Precose” “Glyset”

Answer 50

metformin- Inhibits hepatic gluconeogenesis Increases insulin receptor activity making cells more sensitive to insulin, increased glucose uptake Sulfonylureas – “Glyburide”, “Glipizide” Close ATP-dependent K+ channels in beta cells causing insulin release Alpha-glucosidase inhibitors “Precose” “Glyset” Delays intestinal absorption of carbohydrates- in T2DM is first phase secretion dampened, these alpha slow things down to allow for beta cells to catch up

Question 51

What does amylin do?

Answer 51

Amylin – Released with insulin from vesicles in beta cells Synergistic with insulin in regulation of blood glucose Circulating amylin increased in obesity, hypertension Possibly contributes to beta cell destruction by forming amyloid

Question 52

What are PDX-1 and TCF72 and Neurogenin 3?

Answer 52

PDX-1 important for both islet neogenesis and beta cell proliferation TCF72 downstream targets regulate beta cell proliferation Neurogenin 3 = key for endocrine cell development ISLET CELL DEVELOPMENT

Question 53

What is hirutism? | What is gynecomastia?

Answer 53

hiruitism- male patterned hair growth | gynecomastia- enlarged breast tissue

Question 54

Are there oogonia present at birth? What is the diplone stage part of?

Answer 54

No oogonia are present at birth – all converted to primary oocytes or subject to atresia Arrest due to oocyte maturation inhibitor (OMI) = small peptide secreted by follicular cells diplotene stage is part of prophase (arrest in diplotene phase as a primary oocyte)

Question 55

Patient has very short stature, “shield” chest, webbed neck, and upper torso deformities. Does not go through puberty or have menstrual cycles. Name disease and karyotype.

Answer 55

45, XO KARYOTYPE “gonadal dysgenesis” Turner's syndrome. Both X chromosomes are required during development for oogonia. Ovary becomes a “streak” = fibrous tissue Systemic phenotypic issues due to aneuploidy

Question 56

Karyotype for Kleinfelters?

Answer 56

Klinefelter Syndrome 47, XXY Y chromosome: testes present (small, hyalinated); infertile Testosterone is low (due to testicular dysfunction), micropenis Eunuchoid body: lower segment > upper segment by more than 2”; short arms Gynecomastia – elevated estradiol Systemic phenotypic issues due to aneuploidy often testis not descended… small development of external genitalia (due to lack of DHT) DHT low bc testosterone is low testosterone tends to be converted to estradiol so get breast development and lots of systemic problems bc of anepleudy

Question 57

Describe hormones and phenotype. Complete Androgen Resistance 46, XY

Answer 57

Male Pseudohermaprhoditism Complete: loss of X-linked AR gene Phenotype: female with blind vaginal pouch Y chromosome – induces mullerian duct regression, testes (undescended); lack of androgen effects (no Wolffian duct development, no external genitalia) High estrogens induce development of female body characteristics but no response to androgens so also no Wolf development. no internal male or female structures look female but no internal structures of any kind. infertile high estrogens bc androgens at high levels shunted into pathway to be converted into estrogens.

Question 58

Describe Androgen Resistance 46, XY (partial).

Answer 58

Partial: AR mutation – partially functional Hormones: Androgen levels are high (lack of feedback, estrogen levels high (for male). Gonadotropins? Phenotype: ambiguous with blind vaginal pouch (under masculinized) Y chromosome – induces Mullerian duct regression, testes (undescended); Wolffian duct develops, gynecomastia enough testosterone prod. locally to allow structures to develop but not enough systemically.. Wolf develops so there is still lack of neg. feedback and still gynecomastia bc androgens pref. converted to estrogens.

Question 59

46,XX
 PRENATAL ANDROGEN EXPOSURE 
(not chromosomal abnormality) What is the most common cause?

Answer 59

FEMALE PSEUDOHERMAPHRODITISM Fetal congenital adrenal hyperplasia ** most common Maternal androgen excess Adrenal or ovarian tumors Progestational drugs

Question 60

What does the following describe? Virilization by androgens- advanced skeletal “age”, clitoromegaly and other ambiguities of genital anatomy.

Answer 60

46,XX
 PRENATAL ANDROGEN EXPOSURE 
(not chromosomal abnormality) FEMALE PSEUDOHERMAPHRODITISM child age 5 but bone age, excessive androgen prod. that increases bone age, so acceleration of bone age in child (bones of 9 year old) short… height of 11 year old but is 23… happens w contraceptives during preg. 8-12th week of development, fusion of labia, retention of urogenital sinus

Question 61

Differentiation of external genitalia is highly variable – ambiguous Cryptorchidism and hypospadias What would this be?

Answer 61

XX hermaphrodites generally raised as females. Possible SRY translocation or loss of RSPO1 gene (testes repressor). No spermatogenesis because other Y genes not present. Describe a true hermaphrodite.

Question 62

What is kisspeptin? What would a mutation is KISS1 receptor cause?

Answer 62

Kisspeptin – required to initiate increased GnRH release at the time of puberty. Presumed signal for pubertal onset. Mutations in KISS1 receptor cause hypogonadotropic hypogonadism

Question 63

What is the primary determinant for testis size at puberty?

Answer 63

FSH FSH – Stimulates spermatogenesis Increases sperm motility Stimulates growth of seminiferous tubules – primary determinant of testes size Stimulates androgen binding protein (ABP) – maintains high local T Stimulates aromatase Stimulates inhibin Stimulates growth factors

Question 64

Why might excess T cause CV problems in men?

Answer 64

increase LDL in liver prod. and decrease HDL- could put men at risk for CV problems