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Endocrinology 1.1

UWORLD Endocrine Review

QuestionAnswer
Which thyroid cancer arises from Parafollicular Calcitonin-secreting cell? Medullary Thyroid Cancer
Sheets of polygonal or spindle-shaped cells with extracellular AMYLOID deposits derived from calcitonin, describes the histology of what malignancy? Medullary Thyroid Cancer
Medullary Thyroid cancer is associated with: MEN2A and MEN2B
Medullary Thyroid cancer develops amyloid deposits, thus, it stains: Congo Red
Development of glandular breast tissue in men is? Gynecomastia
What are the 2 factors involved in the development of Gynecomastia? 1. Increased Estrogen to Androgen ratio 2. Ductal Epithelial Hyperplasia and stromal fibrosis
What are common diseases associated with gynecomastia? Liver cirrhosis, Obesity, CKD, hypogonadism, 5-a-reductase deficiency.
To what drugs is the development of gynecomastia associated? GnRH agonists, Ketoconazole, Spironolactone,
How is the fat around internal organs referred as? Visceral Obesity
Visceral obesity is an indicator of: Insulin resistance
TPO is + for: Hashimoto's Thyroiditis
Which are the two most common INCRETINS? GLP-1 and GIP
Are incretins dependent or independent of serum glucose levels? Incretins are independent of blood glucose level
GI hormone released by gut mucosa after the ingestion of a rich glucose meal that increases insulin release? Incretins
What are the two main causes of Hypothyroidism? Pituitary and Hypothalamic lesions/disorders
What are examples of conditions that may provoke Hypothalamic Hypothyroidism? Sarcoidosis, Infection and radiation therapy
Sheehan Syndrome is a common cause of: Pituitary Hypothyroidism
Mass lesions on the Pituitary are known to cause: Hypothyroidism and Tunnel Vision
Low level of hormones released by the pituitary cause deficiency in: ACTH, Thyroid hormone, Gonadotropins
Deficiency in ACTH is clinically manifested as: Hypotension, decreased weight, and hypoglycemia
Hypothyroid patient presents with: Fatigue, cold intolerance, slowed deep tendon reflexes
Low levels of Gonadotropins lead to ___________________ and ______ in the female, and decreased _________________ and also __________ in the male. amenorrhea; infertility; libido; infertility
In 21-(OH) deficiency, there is a deficient conversion of ______________________ into ____________________, which impairs ___________________ synthesis. 17-hydroxyprogesterone into 11-deoxycortisol; Cortisol
Decreased levels of CORTISOL in 21-(OH) deficiency lead to: Increased level of ACTH release by the Anterior Pituitary
Which specific zona of the adrenal cortex is hypertrophied in 21-(OH) deficiency? Z. RETICULARIS, which causes increased levels of Androgens
Elevated sex hormone + low levels of Cortisol and Aldosterone + Low BP, and increased renin activity. Dx? 21-(OH) deficiency
Which congenital Adrenal enzyme deficiency is presented with skin hyperpigmentation? All of them due to increased levels of MSH as it is coproduced with ACTH
If congenital adrenal deficiency starts with "1" --> Hypertension
If congenital adrenal insufficiency ends with "1" --> virilization in females
DECREASED renin activity is seen in which adrenal deficiency? 11-B-Hydroxylase
In congenital adrenal deficiencies the Blood pressure and the [K+] are ____________________________ proportional. Inversely
Fetal DM leads to INCREASED fetal ____________________, that then presents with _____________________, ____________________ cardiomyopathy, and __________________________ after delivery. Insulin; macrosomia; Hypertrophic; HYPOGLYCEMIA
How is Placental vasculopathy caused by fetal DM, presented most commonly? Aphasia, growth retardation, and POLYCYTHEMIA.
What is the main reason for the severe hypoglycemia seen in babies with diabetic mothers? The mother created a state of chronic hyperglycemia, which caused the fetus to create an constant hyperinsulinemic environment, which is not compensated at birth.
Di George Syndrome: 1. Failure of 3rd branchial pouch (inferior PTH) to form 2. Failure of 4th branchial pouch (superior PTH) to form
Signs seen in Di George Syndrome: 1. Chovek Sign (twitch of nose and lips) 2. Trousseau sign (carpal spasm)
Absent Thymic shadow, low levels of T-cells and cleft lips are key characteristics of: Di George Syndrome
Sulfonylureas MoA? Increase INSULIN SECRETION by the Pancreatic-B cells, INDEPENDENT of blood glucose levels.
Where does the sulfonylurea bind in the Pancreatic B-cell? ATP-dependent K+ channel
The attachment of Sulfonylurea to ATP- dependent K+ channel causes _____ ____________, leading to subsequent exocytosis of ___________. Calcium influx; Insulin
What are common Second Generation Sulfonylureas? Glyburide, Glipizide and Glimepiride
1st generation Sulfonylureas? Chlorpropamide and Tolbutamide
What is a common side effect of ALL sulfonylureas? Hypoglycemia and Weight gain
What is an important side effect of 1st generation Sulfonylureas? Disulfiram-like effects
2nd Generation sulfonylureas may cause __________________ as a common side effect. Hypoglycemia
GLP-1 analogues are ___________________. Two very common examples are ____________ and ________________. Injectables; Exenatide and Liraglutide
Linagliptin, saxagliptin and sitagliptin are diabetic control drugs classified as ________________. DPP-4 inhibitors
In DKA the patient has excessive _____________________ breakdown in ___________ tissue due to ____________ deficiency TRIGLYCERIDE; ADIPOSE; INSULIN
What enzyme is responsible for breaking down Triglycerides into Fatty acids? LIPASE
GLYCEROL is broken down in the _______________ by __________ __________, into Glycerol-3-P which then becomes DHAP, which produces _________ via ________________ and __________ via ________. Liver; GLYCEROL KINASE; Glucose via Gluconeogenesis; ENERGY via GLYCOLYSIS
Hyperthyroidism causes the upregulation of ___ -receptors expression, leading to INCREASED ___________________ effect. B-receptors; CATECHOLAMINE
Beta blockers are used in Hyperthyroidism for: 1. minimize the ADRENERGIC effects 2. inhibit 5'-monoiodide, thus decreasing the conversion of T4 into T3.
Beta-blockers in Hyperthyroid patients cause a decrease in T___ production by inhibiting _________________________. T3; 5'-monoiodide.
What is the MC type of Thyroid cancer? Papillary Thyroid cancer
Large cells with nuclei, containing finely dispersed CHROMATIN, giving an empty or "ground-glass" appearance, and intranuclear inclusions, is the histology seen in? Papillary Thyroid cancer
"Orphan-Annie eyes" histological description is seen in what type of thyroid cancer? Papillary Thyroid cancer
Psammoma bodies are seen in what type of Thyroid cancer: Papillary
Laminated Calcium deposits seen in certain malignancies? Psammoma bodies
What are the 2 most common causes of DI? 1. Inadequate PITUITARY secretion of ADH 2. Kidney disease as it fails to respond to ADH
Central DI refers to: Inadequate pituitary secretion of ADH
Nephrogenic DI is due to inability of the collecting duct to respond to _______________. ADH
Administration of analogous ADH produces a positive response in what type of Diabetes Insipidus? Central DI
Post-Pituitary damage produces ___________________ __________ DI. Transient Central DI
Permanent Central DI is caused by: Hypothalamic nuclei damage.
1. Beta-Oxidation of Fatty Acids 2. TCA cycle 3. Carboxylation of Pyruvate (Gluconeogenesis) Processes occuring in the MITOCHONDRIA
Processes occuring in the CYTOSOL: 1. Glycolysis 2. Fatty acid synthesis 3. PPP
The PPP uses: Transketolase and Vitamin B1 as cofactor.
Where does the 1st step in STEROID synthesis occur? all subsequent steps are done in what organelle? MITOCHONDRIA. All other steps occur in the SMOOTH ER
What is a organelle characteristic of all Steroid producing cells? Well developed Smooth Endoplasmic reticulum. (SER)
Which organs have well-developed SER cells? Adrenal glands, gonads, adn liver
Cells that produce steroids: Increase also the androgen production which may lead to virilization and male-hair pattern.
Cushing Disease main hormone abnormality is: High levels of ACTH
High ACTH levels are commonly due to Cushing's, if the ACTH is suppressed after low dose Dexamethasone test, which are the possible causalities of the elevated ACTH? 1. Adrenal adenoma 2. Adrenal malignancy 3. Exogenous glucocorticoid intake (MC) (person with chronic inflammatory disease)
Suppressed levels of ACTH after High dose Dexamethasone Test, indicative which probable causes? Pituitary adenoma
Failure to suppress level of ACTH with Low and High Dexamethasone tests, most probably indicate? Ectopic ACTH production (malignant tumor)
What is the most common Ectopic ACTH secreting tumor? Small Cell carcinoma of the Lung
Inherited enzyme deficiency causing Lactic Acidosis and neurological disorders? Pyruvate Dehydrogenase Complex Deficiency
In Pyruvate Dehydrogenase complex deficiency, the patient is unable to convert ____________________ into __________________. PYRUVATE into Acetyl-CoA
What is the treatment of PD complex deficiency? Purely Ketogenic amino acid diet
Which are the purely Ketogenic amino acids? Lysine and Leucine
Which are the ACTH-Dependent causes of Cushing Syndrome? 1. Cushing Disease --> Pituitary ACTH hypersecretion 2. Ectopic ACTH secretion --> secretion of ACTH paraneoplastic
What is the ACTH-INDEpendent cause of Cushing Syndrome? Adrenal adenoma or carcinoma
Bilateral adrenal hyperplasia involving the Z. Fasciculata and Z. Reticularis. ACTH-dependent Cushing Syndrome changes at tissue level
At time of GLUCOSE DEPLETION, the body uses which substance to create energy? KETONE
________________ metabolism occurs in the ________________ in times of prolonged ________________. Ketone; Liver; Fasting
Which cells are not able to use Ketones for energy at all and why? Red Blood cells because it lacks of Mitochondria
Are ketones regularly used as energy source by the brain? No, the brain cell will only take up ketone for energy in cases in extreme cases.
Essential Fructosuria is due to deficiency of ____________________. FRUCTOKINASE
In Essential Fructosuria, the lack of Fructokinase activity, is compensated by increase activity of _____________________, entering then ___________________. HEXOKINASE; Glycolysis
Deficiency of _________________ leads to development of Severe Fructose inherited intolerance. ALDOLASE B
What is the clinical presentation of Fructose Intolerance? Hypoglycemia and vomit after fructose ingestion , along with Liver and Renal failure.
In the synthesis of Insulin, the ___________________________ is translocated into the _________________, by the ______-____________. PRE-PRO-INSULIN; Rough Endoplasmic Reticulum; N-terminal
What is the role of PRP (signal peptide protein)? cleaves preproinsulin, into PRO-INSULIN enter the Golgi Apparatus.
Once Pro-Insulin is cleaved into ___________________ and ____________ in __________________ amounts in the ______________ _______________. Insulin; C-peptide; Equivalent; secretory granules
Defective Lipoprotein Lipase leads to development of? Familial Chylomicronemia Type 1
What substance is accumulated or elevated in Familial Chylomicronemia? Chylomicrons
What are key features of Type 1 Familial Hyperlipoproteinemia? 1. ACUTE PANCREATITIS episodes 2. Lipemia retinalis 3. Eruptive Xanthomas
Another name for Type 2A Familial Hyperlipoproteinemia? Familial Hypercholesterolemia
What is defective in Type 2A Fam Hypercholesterolemia? 1. LDL receptor 2. ApoB-100
Type ________ hypercholesterolemia is due to _______ receptor or ___________ deficiency or malfunction. 2A; LDL receptor; ApoB-100
Elevated LDL is seen in which hyperlipoproteinemia? Type 2A Familial Hypercholesterolemia
Patient with premature atherosclerosis, TENDON XANTHOMAS, and xanthelasmas, suspect of? Type 2A Familial Hypercholesterolemia
Familial Dysbetalipoproteinemia Type 3 Familial Hyperlipoproteinemia
Defective ApoE leads to what cholesterol disorder? Familial Dysbetalipoproteinemia
In Type 3 Familial Hyperlipoproteinemia, what is the substance accumulated, what is the defective enzyme? Accumulation of: 1. Chylomicrons 2. VLDL remnants Defective ApoE (3 &4)
Type 4 Hyperlipoproteinemia is also known as: Familial Hypertriglyceridemia
Accumulation of VLDL only, is seen in Type _______ hyperlipoproteinemia. 4
Tuberoeruptive and palmar xanthomas are characteristic of? Familial Dysbetalipoproteinemia
What are the xanthomas manifested or characteristic of Type 3 Hyperlipoproteinemia? Tuberoeruptive and Palmar xanthomas
What Familial Hyperlipoproteinemia has LDL and VLDL accumulated? Type 2B Familial Hypercholesterolemia
What are the differences between Type 2A and Type 2B Familial Hypercholesterolemia? Type 2A is mainly LDL receptor deficient and accumulates LDL, while Type 2B has LDL receptor and ApoB-100 defective and accumulates LDL and VLDL
______________ deficiency, has low CORTISOL and excessive release of _________________. The best treatment is __________________ corticosteroids, in order to suppress ______________ production. 21-(OH); ACTH; Exogenous; ACTH
The excess ACTH seen in 21-(OH) deficiency leads to? Decreased androgen production, which manifests with a DELAY in SEXUAL development.
RET mutation + Increase Calcitonin + Marfanoid Habitus. Dx? MEN 2B
What are the neoplasms associated with MEN2B? 1. Oral/ Mucosal Neuromas 2. Medullary Thyroid cancer 3. Pheochromocytoma
Patient with multiple benign submucosal neoplasm, episodic tachycardia, and serum calcium below normal, and a similar history seen in the father of patient. Dx? MEN2B
Where are the Cortisol receptors located? Cytoplasm
_________________ is different to many of is class of hormones, because it has its receptor in the __________________, and not in the ______________ as normally would be expected. CORTISOL; Cytoplasm; Nucleus
Cortisol is translocated to the ______________ after binding to receptor in the ________________. Once in the _____________, it gets __________________ and enhance hepatic ___________ production. NUCLEUS; Cytoplasm; Nucleus: transcribed (transcription); glucose
High levels of Cortisol = High levels of Hepatic GLUCOSE synthesis --> Hyperglycemia.
Aromatase Inhibitors include: Anastrozole and Letrozole
Enzyme inhibited by Anastrozole? Aromatase
______________________ is enzyme that carries the conversion of ______________________ into ________________. Aromatase; Testosterone: Estradiol
What type of malignancy is treated with Aromatase Inhibitors? ER-2 + Breast cancer
Cholesterol is converted into Pregnenolone in the ________________, and all subsequent steps in Estrogen synthesis occur in the _____________________________. Mitochondria; SMOOTH ENDOPLASMIC RETICULUM
What is the most important INSULIN stimulator? Glucose
Glucose in Pancreatic B-cell undergoes _____________________ to produce _________, which then binds to the _______________________. GLYCOLYSIS; ATP: ATP-sensitive K+-channel, allowing for depolarization and subsequent INSULIN release from cell.
Anatomically, the ANTERIOR pituitary is just BELOW the __________ ______________, and it drops _____________ than the ____________ pituitary. Optic Chiasm; Lower; Posterior
Exogenous Insulin demonstrates levels of: Elevated Insulin with DECREASED C-peptide
If insulin and C-peptide are both elevated, and there is a Positive drug assay, suspect? Drug intoxication by person with access to Diabetic drugs (oral hypoglycemics)
An Insulinoma: Produces Elevated Insulin and Elevated C-peptide, with negative drug assay.
Injectable Insulin does NOT increase ____________________ C-peptide
Initially, the Increase in Estrogen during pregnancy will lead to a ______________ free ______. DECREASE; T4
Estrogen's high levels in pregnancy also cause, an increase in _________ and bound ________, but decrease in free ______. The increase _________ _______ promotes the release of new _______ hormone to restore levels of free ______. TBG: T4: T4; bound-T4; TRH; T4.
What enzyme converts Testosterone into DHT> 5-alpha-reductase
What is DHT's role? Development of External MALE genitalia in the Fetus
A male patient with 5-alpha-reductase deficiency will show: Feminized External Genitalia, until puberty
What are 2 conditions highly associated to 5-alpha-reductase deficiency? 1. HYPOSPADIAS 2. Small phallus
What drug inhibits 5a-reductase? Finasteride
By which GLUT is glucose taken into the cell in muscle cells and adipocytes? GLUT-4
Which GLUT is INSULIN dependent? GLUT-4
Which GLUT is insulin INDEPENDENT? GLUT 1, 2, 3, and 5
As the concentration of insulin increases the expression of GLUT-4 ____________________, and the expression of GLUT____________ remains the same. INCREASES; GLUT 1, 2, 3, 5
What is the MCC of Adrenal Insufficiency? Hypothalamic-Pituitary-Adrenal suppression by Glucocorticoid therapy.
What are some common triggers/situations/events that lead to an adrenal crisis? Times of high stress, such as surgery and/or illness.
What are the labs seen in Adrenal Crisis? Low Cortisol, Low CTrH, and low ACTH
Patient with decreased cortisol, ACTH and CTrH, is about to enter the OR for cholecystectomy. What is a common cause for the patients laboratory results? Adrenal Crisis
Conversion of Oxaloacetate into PEP by using PEP carboxykinase (PEPCK) First step of GLUCONEOGENESIS
What is the cofactor used in the first step of Gluconeogenesis? GTP is the cofactor used by PEPCK in GLUCONEOGENESIS
From which cycle is the GTP used in Gluconeogenesis originated? From the TCA cycle, as Succinyl-CoA converts into Succinate.
What hypothalamic hormone inhibits Prolactin? Dopamine
Dopamine inhibitors may cause: Hyperprolactinemia
What two hypothalamic substances stimulate the release of Prolactin? TRH and VIP
Haloperidol is a ________________ inhibitor that may cause: Galactorrhea
Small Vessel Leukocytoclastic Angiitis is associated with ________, in children 3-11 years old, by deposition of _________ adn _______. HSP: IgA and C3
Hepatitis C Associated with Leukocytoclastic Vasculitis
What is Leukocytoclastic Vasculitis? Small Vessel Vasculitis that affects most evidently the skin
Skin lesions (multiple red dots) + arthralgias + recent treatment with a Beta-lactam, and the patient got symptoms resolved spontaneously. Small Vessel Leukocytoclastic Vasculitis
Conn's Syndrome: Primary HyperALDOSTERONISM
What is the MCC of Conn's Syndrome? Bilateral Adrenal Hyperplasia
Patient presents with HTN, low serum[K+], pH higher than 7.45, muscle fatigue and paraesthesias, with abdominal CT showing abnormally large adrenal gland. Dx? Conn's syndrome
Elevated plasma Aldosterone and Low plasma RENIN activity. Dx? Conn's syndrome
The muscle weakness and paresthesias seen in Conn's Syndrome, are due to: Severe hypokalemia
Inappropriately high activity of renin-angiotensin-aldosterone system, is the MCC of: Secondary Hyperaldosteronism
Baby presents with Enlarged fontanelle, Protruding tongue, and Umbilical hernia, and mother states is hard to feed. PE shows mild jaundice. Dx? Congenital Hypothyroidism
What are the 3 most used descriptions for Congenital Hypothyroidism? 1. Enlarged Fontanelle 2. Protruding tongue 3. Association with UMBILICAL hernia
The brain, kidneys, intestines, liver and RBCs use what type of GLUT transporters? Insulin-INDEPENDENT GLUT
RBCs and BBB use which GLUT? GLUT-1
GLUT-2 is used by: Hepatocytes, B-pancreatic cells, and basolateral layer of renal tubule
The ____________ and ________________ transport use GLUT ___ for glucose uptake. Placenta; Neuronal; 3
GLUT-5 is used by: Sperm and GI tract
An increase in Insulin cause NO upregulation of GLUT expression. Insulin-INDEPENDENT GLUT
Insulin-Dependent GLUT Increase in INSULIN causes an UPREGULATION of GLUT-4 expression.
What is the main role of PTH? Increase BONE RESORPTION to increase serum Calcium
PTH acts INDIRECTLY on_______________________ and DIRECTLY on the ________________________. Osteoclasts; OSTEOBLASTS
Osteoblasts have ____________ receptors PTH
The binding of PTH and osteoblast leads to: Increased production of RANK-L and M-CSF
As ______________ and M-CSF combine, after PTH was bounded PTH-receptor on Osteoblast, it lead to the maturing of ___________________, lead into to an increase bone______________. RNK-L; Osteoclasts; Resorption
RANK-L? product from PTH and Osteoclast interaction. Associated with elevated levels of PTH and low level of serum Calcium.
What are the common Fast-acting Insulins? Aspart, Lispro, and Glulisine
Regular Insulin's effect is completely gone after how many hours approximately? 7 hours
Which effect is longer, NPH or Detemir? Detemir insulin actions act up to 24 hours, while NPH's act up to 18 hours.
Insulin receptor shows: Tyrosine Kinase activity
What are common side effects of Insulin preparations? 1. Hypoglycemia 2. Lipodystrophy 3. Hypersensitive reactions
What happens in the liver as insulin is uptaken? Increase glucose store as GLYCOGEN
Increase in glycogen and protein synthesis, is seen as: Insulin actions in the MUSCLE
How is fat affected upon contact with Insulin release: Increase Triglyceride storage
Regular Insulin is considered __________ acting, while__________ is intermediate acting insulin. SHORT; NPH
What is a desired or advantageous side effect of Metformin: Loss of weight
What are the MoA of Metformin? 1. Inhibits mGPD, which causes inhibition hepatic gluconeogenesis and the action of glucagon. 2. Increases glycolysis 3. Increases peripheral glucose uptake (increases insulin sensitivity)
Biguanide Metformin
Where does the B-oxidation of FA occurs? Mitochondrial matrix
Transported used by Fatty Acids to move across the membrane Carnitine
Main product of the de novo fatty acid synthesis first step? Malonyl-CoA
______________ inhibits the transport of _______________ by carnite and ______________________. Malonyl-CoA; Fatty acids; carnitine acyl-transferase
Malonyl-CoA: 1. Major product of the de Novo FA synthesis first step 2. Inhibits carnitine acyltransferase --> no Fatty acid across membrane of the mitochondria.
Endometrial tissue outside the uterus. Endometriosis
Chronic endometriosis lead to the formation of ______________ which cause ______ of the ________________ tubes, leading to ___________________. ADHESIONS; scarring; Fallopian: INFERTILITY
What are the 3 main causes of abnormal vaginal bleeding? Fibroids, Adenomyosis, and Endometrial cancer/hyperplasia.
25 yo female. presents with heavy menses, constipation, frequent urination. She states pelvic pain, and a sensation of "something pulling down" in the pelvic area. PE shows very enlarged uterus. Dx? Fibroids
Fibrinoid key features: 1. Heavy menses 2. Pelvic pain/heaviness "pull-down" sensation 3. Enlarged uterus
Pelvic examination demonstrates a bulky, globular, and tender uterus, and a 7 month Hx of dysmenorrhea. Dx? Adenomyosis
What is a common risk Hx for a patient to develop Endometrial carcinoma> Hx of Obesity, null parity, or chronic ovulation.
69 yo female complains of vaginal bleeding. Her last menses was over 10 years ago. She has a indicates past gastric bypass surgery 20 years ago, and hysterectomy at age 21. Dx? Endometrial carcinoma/hyperplasia
Most common cause of vaginal bleeding in postmenopausal women? Endometrial carcinoma/hyperplasia
Difference in uterus Physical examination in Fibroids, Adenomyosis, and Endometrial cancer? Fibroids have enlarged uterus. Adenomyosis have bulky, globular and tender uterus Endometrial cancer have a NON-tender uterus.
DKA is a common cause of: Metabolic acidosis
What is adenomyosis? Condition in which the endometrium (inner lining of uterus) breaks through the Myometrium (muscle wall of uterus), causing vaginal bleeding.
DKA produces a ______________ odor in the _______________ and ______________. Fruity; breath ; urine
Sudden onset of polyuria, polydipsia, volume depletion and fruity odor in breath. Dx? Diabetic Ketoacidosis
Compensation of metabolic acidosis is ________________________, which is done by ____________________________. respiratory alkalosis; HYPERVENTILATION
What are common causes of Adrenal insufficiency? Adrenal hemorrhage or infarct, and acute onset of illness or surgery.
What is the treatment for adrenal insufficiency? Common used medication? The use of glucocorticoids; Dexamethasone
Thyrotoxicosis labs show: 1. Elevated free T4, 2. Suppressed TSH 3. Decreased weight
Tremors, suppressed TSH, elevated T4, and loss of weight, describe the clinical profile of which hormonal disorder? Thyrotoxicosis
How is the histology of Exogenous Hyperthyroidism described: Atrophic thyroid follicles, decrease in colloid, and low/undetectable thyroglobulin.
Thyroid tissue biopsy demonstrates LYMPHOCYTIC infiltrate with GERMINAL centers. Hashimoto's Thyroiditis
De ____________ thyroiditis has disruption of follicles and _________ cellular infiltrate with _____________________________ cells. Mixed; Multinucleated Giant cells
What is the histological finding in Grave's disease? Tall, columnar epithelium with scalloped margins of colloid.
What are zinc-motifs? The most common DNA-binding domain.
What is the composition of Zinc-motifs? chains of amino acids, which mostly include Cysteine and Histidine, around central Zinc atom
Which amino acids compose Zinc-motif? Cysteine and Histidine
Transcription factors, steroids, thyroid hormone, adn fat-soluble vitamins, commonly use ____________________ as their DNA-binding domain. Zinc - motifs
Which autoimmune conditions have higher risk of developing in a patient with DM type 1? Hashimoto's thyroiditis, Grave's disease, and Addison's disease.
DM type 1, Hashimoto's, Graves' disease and Addison's disease all are _____________. HLA-2
What are the electrochemical imbalances of Addison's disease? 1. HYPOnatremia 2. HyperKalemia and Hyperchloremia 3. Non-anion gap metabolic acidosis
Addison's Disease is also classified as: Chronic Primary Adrenal Insufficiency
Addison's Disease has __________________ gland dysfunction, leading to decreased levels of both, ________________ and ____________________. Adrenal; Cortisol and Aldosterone
The hyponatremia seen in Addison's disease accounts for the clinical presentation of _______________________. Hypotension
Patients with Addison's have increased production of ________ as it made with ACTH, and causes ________________________ of the skin. MSH; HYPERPIGMENTATION
What is a common cause of PRIMARY ACUTE adrenal insufficiency? Waterhouse-Friedshensen Syndrome
__________________________ is often caused by __________________ by N. _____________, __________, or _______________________ shock. It causes adrenal gland ________________________. Waterhouse-Freidshensen Syndrome; Septicemia: N. meningitis; DIC: Endotoxin; hemorrhage.
Main differences between PRIMARY and SECONDARY adrenal gland insufficiency? Secondary adrenal insufficiency is caused by pituitary gland inability to produce ACTH, while Primary is due to Adrenal gland dysfunction. In Secondary Adrenal Insufficiency, there is no Hyperkalemia and no skin pigmentation.
Abrupt withdrawal of exogenous steroid use, may produce ____________________ adrenal Insufficiency. Tertiary
The Leydig cell is stimulated by ________, which in turn secretes__________________. LH: secretes Testosterone
By what cell is Testosterone secreted? Leydig cell in the Testis
Testosterone is secreted by Leydig cells in the testes by stimulation of which Pituitary hormone? LH
What substance is secreted by Sertoli cells in the testes with FSH stimulation? Inhibin B
Testosterone INHIBITS both, the ___________________ and _______________ release of GnRH and LH, respectively. Hypothalamus: Pituitary gland
Unlike Testosterone, Inhibin B, only inhibits the release of ______ in the __________________ gland. FSH; Pituitary gland
What is the main function of T-cells and NK cells? Anti-cancer
Which are the two main cancer in which T-cells and NK cells act upon or attack? Melanoma and Renal Cell carcinoma
-- B-cell -- No memory -- Short duration -- NO immunogenicity in infancy Polysaccharide vaccine
Protein-Conjugated vaccine characteristics: + B/T-cell immunity (Humoral and Cellular) + Memory + Long Duration + Immunogenicity in infancy
Passive immunization: Receiving PREFORMED antibodies -- Rapid onset and short half-lives (3 weeks)
Examples of passive immunization IgA breast milk, maternal IgG crossing the placenta, antitoxin, humanized monoclonal antibody.
What is Active Immunity means of acquisition? Exposure to foreign antigens
What type of immunity has a slow onset and creates memory? Active immunity
Natural infections, vaccines, toxoids Examples of active immunity
Preformed antibodies, may be given to a patient that had recent exposure to which toxins or infections? What is the main benefit? This process is Artificially-acquired Passive Immunity. Done after exposure to Tetanus toxin, Botulinum toxin, HBV, Varicella, Rabies Virus, or diphtheria toxin. Provides a quick or prompt healing.
What is the most common treatment for anaphylactic shock? Epinephrine
Symptoms seen in Anaphylactic shock? Vasodilation, increased vascular permeability, and bronchoconstriction.
What is the virulence factor of Strep Pyogenes? M-protein.
Scarlet Fever is caused by what common organism? Group A strep (S. pyogenes)
Pentad of; 1 Fever, 2 pharyngitis, 3 Strawberry-tongue, 4 sand-paper like skin rash, 5 circumoral pallor, describes the clinical manifestation of? Scarlet Fever
Infection of S. pyogenes, with or without development of Scarlet Fever, predisposes a higher risk for development of what 2 other conditions? 1. Rheumatic Fever 2. Glomerulonephritis
Patient with Kawasaki Disease has a higher risk of development of _____________________________. Coronary Aortic Aneurysm
Increased cleavage of C2 and C4, resulting in inappropriate activation of the complement cascade is seen in? C1 deficiency, which is a common cause of Angioedema
The conversion of Kininogen to Bradykinin in C1 deficiency, is done by: C1INH
High levels of ______________________ in Hereditary _______________, are seen due to low levels of __________________________. Bradykinin; Angioedema; C1 esterase inhibitor
What and why, type of medications are highly contraindicated in Hereditary Angioedema patients? ACE INHIBITORS as these increase Bradykinin levels as a side effect, furthering the angioedema.
Multiple Endocrine Neoplasia are all autosomal ______________ disorders. Dominant
What is the most common Pancreatic tumor seen in MEN1? Gastrinoma
Pancreatic tumor, rarely seen in MEN1, characterized by electrolyte abnormalities and watery diarrhea? VIPoma
What type of thyroid cancer is shared by MEN2B and MEN2A? Medullary
Pheochromocytomas are seen in which two MEN syndromes? MEN2A & MEN2B
Pituitary adenoma + PTH neoplasia + Insulinoma MEN1
Primary PTH hyperplasia + Medullary thyroid cancer + adrenal gland mass + episodic tachycardia MEN2A
MEN 2B Oral mucosa masses + skin neuromas + episodic and recurrent increased heart rate + thyroid cancer
Thin, tall guy, with long arms, but not a swimmer. Complains of episodes of headache and rapid pulses, and several small masses in the inside of the mouth. Recalls mother has similar symptoms. MC Dx? MEN 2B
What enzyme is expressed in granulomatous diseases such as Sarcoidosis, and how is it related to increased levels of serum Ca2+? Sarcoidosis and other granulomatous diseases activate MACROPHAGES, which then express 1a-HYDROXYLASE, which leads to synthesis of 1,25-(OH)2 Vit D and Hypercalcemia
What GI autoimmune disorder is a cause of Secondary Hyperparathyroidism? Celiac Disease
Celiac Disease impairs the absorption of fat-soluble vitamins, such as Vitamin _______, which leads to: ______________ serum __________ and _____________ serum ____________, and __________ serum _______. Vitamin D; low serum Phosphorus; Increased Serum PTH; Low serum Calcium.
Low vitamin D has: Low urinary phosphorus
Why do babies born with non-salt wasting 21-(OH) deficiency are taller? Increased androgens enhance early linear growth.
What's the treatment for 21 - (OH) deficiency? Low doses of EXOGENOUS corticosteroids to suppress excessive ACTH and reduce stimulation of Adrenal cortex.
Females with 21-(OH) deficiency are seen with: Ambiguous genitalia
Increased numbers of catecholamines: Adrenal MEDULLA hyperplasia
Leydig Cell Hyperplasia: Excessive: Testosterone, Androsterone, and DHEA No increase in 17-(OH)
No increase in 17-(OH) with Cortisol dominant symptoms: Pituitary adenoma
Increased FSH, LH. Normal 17-(OH) Excess Cortisol (dominant Cushing Disease symptoms) Pituitary adenoma
What is the key characteristic of MCAD deficiency? Hypoketotic Hypoglycemia
Medium-chain acyl-CoA dehydrogenase deficiency is a disorder of which metabolic process? Beta-Fatty Acid oxidation in the mitochondria
What are the most significant clinical manifestations of MCAD deficiency? 1. HYPOKETOTIC HYPOGLYCEMIA 2. Seizures and sudden death
Fatty acid disorder that presents with Hypoketotic Hypoglycemia, muscle weakness, CARDIOMYOPATHY, and hypertriglyceridemia. Primary Carnitine deficiency
Contrary to MCAD deficiency, which occurs in the _______________, Primary Carnitine deficiency occurs in the ____________________. Mitochondria; Cytoplasm
Patient recently diagnosed with depressive disorder, complains of weakness, very concentrated urine, Dx? SIADH
Most common malignancy associated with development of SIADH? Small Cell carcinoma of the Lung
What is the normal urine osmolarity? 100 mOsm/Kg
1. Ectopic ADH (small cell lung ca) 2. CNS disorder/Trauma (meningitis, SAH) 3. Pulmonary disease 4. Drugs (cyclophosphamide, SSRIs) Common causes of SIADH
Peripartum hemorrhage causing ischemic necrosis, is known as? Sheehan Syndrome
How is Sheehan Syndrome often presented? Mother's delay to lactate, due to Prolactin deficiency.
Why is the reason for developing Sheehan Syndrome? During pregnancy there is an increase n estrogen due to enlargement of pituitary gland, but there is NO proportional blood supply to the gland enlargement.
Another name for De Quervain's Thyroiditis? Subacute Granulomatous Thyroiditis
De Quervain's is most commonly seen after a _______________. viral infection
Is de Quervain's thyroiditis painful? Yes, it is painful
What are some characteristics of De Quervain's Thyroiditis? 1. Transient Hyperthyroid symptoms 2. Increased ESR and CRP 3. Decreased in radioiodine uptake.
Autoimmune, Painless thyroid enlargement, dominant hypothyroid symptoms, +TPO, and histology shows lymphocytic infiltrate with germinal centers Hashimoto's Thyroiditis
Hurthle cells are seen in histology of _____________________________. Hashimoto's Thyroiditis
How are the eosinophilic epithelial cells seen Hashimoto's thyroiditis called? Hurthle cells
Potassium iodine main action? Inhibition of radioactive iodine.
When is the use of Potassium iodine commonly used? In nuclear accidents in order to prevent radiation-induced thyroid carcinoma
Development of Cushing's that ACTH's and Cortisol production is only suppressed by High-dose Dexamethasone test? Pituitary adenoma
Ectopic ACTH secreting adenoma: ACTH cannot be suppressed with low or high dexamethasone tests.
What is the most common Pituitary adenoma, related to High-Dexamethasone suppression-only ? Prolactinoma
_________________ thyroid caner, is the most common type of thyroid cancer. Papillary
"Orphan Annie eyes" cytoplasm in thyroid cells, indicate Papillary Thyroid cancer
Common risk factor, other than family hx, for Papillary thyroid cancer? Radiation Exposure
RET/PTC rearrangements and BRAF mutations lead to increased risk of developing? Papillary Thyroid cancer
Follicular thyroid carcinoma has a ___________ prognosis. It invades the thyroid ___________________ and vasculatures, and is associated to _______ mutations and _________________ translocations. GOOD; capsule; RAS; PAX8-PPAR-gamma
Parafollicular cells are found in which type of thyroid cancer? Medullary Thyroid cancer
Medullary thyroid cancer cells stain + for ________________________. Congo red
RET mutations: MEN2A and MEN2B
To what autoimmune condition is thyroid lymphoma associated? Hashimoto's Thyroiditis
What are common causes of Secondary Hyperparathyroidism? Vitamin D deficiency, decrease Ca2+ uptake, and Chronic Renal Failure
Hyperplasia, adenoma, and carcinoma of the PTH-gland are? Causes of Primary Hyperparathyroidism
Poor prognosis thyroid malignancy, associated with Pleomorphic cells and biphasic spindle cells? Anaplastic Thyroid cancer
Thyroid malignancy with POLYGONAL or spindle shaped cells and + for calcitonin. Medullary Thyroid cancer
Glucocorticoid therapy a predisposal to ultimately induce a chronic state of ________________________________. Hyperglycemia
Glucocorticoid therapy increases the hepatic synthesis of _____________________ and ___________________ proteins to increase the __________________________ availability. Glucogenic and glycogenic; Glucose
An ________________________ effect is seen in glucocorticoid therapy. Anti-insulinic
What changes occur in adipose tissue in patient with glucocorticoid medications? Lipolysis and altered fat distribution
In glucocorticoid therapy, the side effects cause changes in different tissues, such as, Bone, Immune system, Skeletal muscle, liver, skin? Bone --> osteoporosis, Immune system --> suppression and T-cell apoptosis, Liver --> increased gluconeogenesis and glycogenesis, Skeletal muscle and Adrenal cortex --> atrophy, and the skin is thinning, striated adn impaired wound healing.
What enzyme stimulates GLUCONEOGENESIS by increasing the activity of Pyruvate carboxylase? Acetyl-CoA.
Hyperthyroidism causes an ___________________________, characterized by: _______________________________ and hyperreflexia. Hyper-adrenergic; Hypertension, palpitations, tachycardia, sweating, heat intolerance, tremor.
What antiarrhythmic medication type is used in Hyperthyroidism? SE? Beta-blockers to minimize adrenergic effects They do not work on exophthalmos
What are 2 common medications used to treat Hyperthyroidism? Methimazole and PTU
Agranulocytosis Side effect of Methimazole and PTU
___________________ is a teratogenic drug during the ________ trimester. Methimazole; First
What is the main side effect of PTU? Hepatic failure
The use of radioiodine ablation in treatment of Hyperthyroidism may worse the _______________________ seen in these patients. Exophthalmos
Surgery of the thyroid gland is a good option for permanent treatment of hyperthyroidism, but, it may also cause _____________ damage, leading to the development of ____________________ of the voice. Recurrent Laryngeal Nerve; Hoarseness
Acetyl-CoA ---------------------------------> Malonyl-CoA, is catalyzed by what enzyme? Cytosolic Acetyl-CoA carboxylase
What is the main action of Malonyl-CoA? Inhibition of B-oxidation of newly formed fatty acids
What enzyme is inhibited by Malonyl-CoA? mitochondrial carnitine acyltransferase
______________________ is known as a __________________ of the de Novo Fatty acid synthesis and ___________________ of Fatty acids. Malonyl-CoA: REGULATOR ; Beta-oxidation of FA
Events leading to Adrenal Crisis: 1. Prolonged use of glucocorticoids leads to, 2. Suppression of HPA-axis ---> ---> ADRENAL INSUFFICIENCY, 3. In these patients, increased levels of STRESS lead to, ADRENAL CRISIS.
What situations are associated with increased stress leading to adrenal crisis? A person in route to surgery or diagnosed with a severe disease.
A person with known Addison's disease, is about to have knee surgery. The physician should adequately _____________________, in order to prevent Adrenal crisis. Increase the dosage of glucocorticoids
Stimulation of orbital fibroblast by Thyrotropin receptor antibodies and cytokines released by T -cells, leads to development of? Grave's Ophthalmopathy
What is the triad of symptoms seen in Grave's Ophthalmopathy? Exophthalmos, proptosis, and diplopia
____________________ are most widely used in treatment of _________________ (vision condition) Glucocorticoids; Grave's Ophthalmopathy
Which agents use Protein Kinase A, G-protein adenylate cyclase second messenger? TSH, glucagon, adn PTH
The _____ is the major product of the TH gland. T4
What is the active form of thyroid hormone? T3
T3: active form of TH
rT3 is: inactive form generated by peripheral conversion.
G protein-coupled receptors include: TSH, LH, and FSH.
What are 3 major domains of G protein-coupled receptors? 1. Extracellular N-terminus 2. Transmembrane domain 3. Intracellular C-terminus
What type and which amino acids make up the Transmembrane domain G protein-coupled ? HYDROPHOBIC; Ala, Leu, Phe, Trp, Met, Pro, and Gly
Tamoxifen is used in gynecomastia because? Inhibits the effects of ESTROGEN on breast tissue.
Hyperlipidemia associated with eruptive and palmar xanthomas? Familial Dysbetalipoprotenemia
Actions of TPO: 1. conversion of iodide --> iodine 2. Iodination of thyroglobulin tyrosinase residues and, 3. iodotyrosine coupling reaction that forms T3 and T4.
Niacin of MoA: 1. Decrease hepatic synthesis of triglycerides and VLDL, 2. Reduce clearance HDL
hyperlipidemic drug that may cause GOUTY ARTHRITIS? Niacin
Glycogen Storage disease type 2? Pompe disease
Pompe's disease has deficiency of __________________________ Acid alpha-glucosidase (acid maltase)
Patient seen with cardiomegaly, hepatomegaly, generalized hypotonia, and macroglossia. Dx? Pompe Disease
Created by: rakomi