High Yield Topics-Endocrine Flashcards
The type of vitamin D that is obtained from exposure of skin to sun or through ingestion from dairy products
vitamin D3 (aka. Cholecalciferol)
The type of vitamin D that is obtained from ingestion of plants, fungi, and yeasts
vitamin D2 (Ergocalciferol)
- STUDY AID: think of ERGOsterol in FUNGAL cell membrane
Both cholecalciferol and ergocalciferol convert into what storage and active forms?
- 25-OH D3 (storage form)
- 1,25-(OH)2D3 (active form; calcitriol)
cholecalciferol and ergocalciferol convert into storage form in what organ?
liver
cholecalciferol and ergocalciferol convert into active form (calcitriol) in what organ?
kidney (PCT)
Why is vitamin D required to increase serum Ca+2 level?
Active Vitamin D increases intestinal absorption of Ca+2 (and PO43- also)
Enzyme that converts inactive/storage form (25-hydroxyvitamin D) to active form (1,25-dihydroxyvitamin D)
1α-hydroxylase
- mainly in the kidneys
A disorder causing ↑ β-adrenergic receptor expression, leading to ↑ catecholamine effects; presents with SYSTOLIC hypertension, sweating, hot intolerance, diarrhea, warm/moist skin, palpitations/tachycardia, weight loss, hyperreflexia, and can mimic anxiety disorder
Hyperthyroidism
An autoimmune disordercaused by thyroid-“stimulating” antibody that binds and stimulates TSH receptors on thyroid; presents with hyperthyroid symptoms
Graves Disease
Caused by orbital fibroblasts
and T-Cells activation by thyrotropin (aka. TSH) receptor antibodies –> cytokine release (TNF-a, IFN-Y) –> glycosaminoglycan (GAG) deposition in eyes –> expansion/inflammation of extraocular muscles –> exophthalmos (protruding eyes)
Graves Ophthalmopathy
Lab findings of Hyperthyroidism
TSH, T4, T3, TBG
TSH:↓
T4: ↑
T3: ↑
TBG: normal
Improve Graves ophthalmopathy by decreasing the severity of inflammation and reducing the excess extraocular volume
Glucocorticoids
Caused by accumulation of GAGs in leg skin due to activation of dermal fibroblasts by thyroid-stimulating antibodies
Pretibial myxedema
The adrenergic receptor symptoms (systolic hypertension, sweating, hot intolerance, palpitations/tachycardia, hyperreflexia) can be relieved by what drug?
β blockers
Drugs that ↓ the formation of TSH (thyrotropin) via inhibition of thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosines
Thioamides
- methimazole
- PTU
Which Thioamide also decreases the peripheral conversion of T4 to T3?
PTU
A serious complication of Thioamides that results in granulocyte destruction and consequent neutropenia; initially presents with fever, sore throat, and oral ulcerations
Agranulocytosis
If drug-induced agranulocytosis is suspected, what should be done?
Discontinue the drug and obtain CBC w/ diff to confirm diagnosis
A condition characterized by ↑ free T4, suppressed TSH, and low/undetectable TG; occurs with surreptitious levothyroxine abuse, use of animal-sourced thyroid supplements, and erroneous dosing of thyroid replacement therapy
Exogenous Hyperthyroidism
aka. Thyrotoxicosis
The lack of TSH stimulation continued by Exogenous Hyperthyroidism (levothyroxine) can lead to
ATROPHIC thyroid follicles
The main regulator of lipid metabolism by stimulating the mobilization and degradation of lipids (TG)
Thyroid hormone
- TH ↓TG
HLA (Human MHC) associated with Graves disease (2)
- HLA-DR3
2. HLA-B8
Caused by hyperfunctioning follicular cells (hot nodules) due to TSH receptor mutations and not due to increased TSH; ↑ release of T3 and T4
Toxic Multinodular Goiter
(Hot/cold) nodules produce excess thyroid hormone, show up on the scan because they take up more of the isotope than normal thyroid tissue, and almost always are NONcancerous
Hot nodules
(Hot/cold) nodules take up less of the isotope and ARE cancerous
Cold nodules
Occurs when hyperthyroidism is left untreated and gets worse during stress (surgery, infection); presents with fever, diarrhea, delirium, and tachyarrhythmia
Thyroid Storm
The condition that occurs when large amount of excess iodide (counterintuitive) is given as a tx for thyroid storm or thyrotoxicosis –> inhibits thyroid hormone synthesis
Wolff-Chaikoff Effect
What is hyperthyroidism that occurs following administration of iodine in a patient with iodine deficiency or autonomous nodule (nodule that autonomously produce thyroid hormone)?
- Opposite of Wolff-Chaikoff Effect
Jod-Basedow Effect
Autoimmune disorders (Graves , Hashimoto’s) and iodine deficiency cause (smooth or diffuse/nodular) goiter
smooth or diffuse
Toxic multinodular goiter and thyroid adenoma/cancer/cyst cause (smooth or diffuse/nodular) goiter
nodular
Benign solitary growth of thyroid that are nonfunctional (cold)
Thyroid adenoma
Histological finding of thyroid adenoma
Follicular (follicle-like)
Primarily produced by conversion from T4 in PERIPHERAL tissues; has a short ½ life
T3
Hypothyroidism causes ↓ expression of ____ receptors in the liver, leading to ↓ clearance of ____ and ↑ blood ____ levels
- ____ is all same
LDL
Hypothyroidism causes ↑ level of _____ , which ↑ the risk of coronary atherosclerosis
TG
The thyroid releases ___ and ____ in response to ____ from the pituitary, which is regulated by _____ from the hypothalamus
- T4 & T3
- TSH
- TRH
The most sensitive test for thyroid function; first to be outside the normal range in thyroid dysfunction
Serum TSH level
low TSH, low T3, low T4
Presents with myalgias, proximal muscle weakness, delayed relaxation of deep tendon reflexes, and “↑ CK” (creatine kinase) level due to hypothyroidism; diagnosis made by ↑ TSH
HYPOthyroid Myopathy
Inactive form of Triiodothyronine
rT3 (reverse T3)
- T3 is the active form
Ischemic necrosis of the pituitary gland (esp. anterior) that is typically caused by systemic hypotension during DELIVERY; may present with hypothyroidism and deficiency of other pituitary hormones
Sheehan Syndrome
_______ increase serum T4-binding globulin (TBG), thereby increasing serum total T4 concentrations; serum FREE (biologically active) T4 concentration remain normal via negative feedback
estrogen (pregnancy)
Biologically active T4 (thyroxine) is (bound/free)
free
An autoimmune disorder caused by antibodies against thyroid peroxidase (TPO) and thyroglobulin (substrate needed to make thyroid hormone); present as hyperthyroid early in course due to follicular rupture causing ↑ thyroid hormone release
Chronic Lymphocytic Thyroiditis
aka. Hashimoto
Histologically presents with lymphocytic infiltrate with germinal centers
Chronic Lymphocytic Thyroiditis
aka. Hashimoto
Large, pink-staining cells filled with granular cytoplasm seen in Hashimoto’s
Hürthle cells
- STUDY AID: “H”urthle cells for “H”ashimoto’s
HLA (Human MHC) associated with Hashimoto’s (2)
HLA-DR3
HLA-DR5
Hashimoto’s increase the risk of what lymphoma?
non-Hodgkin lymphoma
Fetal hypothyroidism caused by maternal hypothyroidism, thyroid dysgenesis, or iodine deficiency; presents with pot-bellied, puffy face, macroglossia (big tongue), big umbilicus, and poor feeding
Congenital hypothyroidism
Congenital hypothyroidism is aka.
Cretinism
A self-limiting condition following a viral illness like flu; presents with ↑ ESR and PAINFUL thyroid enlargement
Subacute Granulomatous Thyroiditis
Subacute Granulomatous Thyroiditis is aka.
(de Quervain)
- STUDY AID: Quer”vain” for “pain”
Histological finding of Subacute GRANULOMATOUS Thyroiditis (de Quervain)
Granulomatous Inflammation (resembles granulomas)
- Inflammatory infiltrate w/ macrophages and multinucleated giant cells
A self-limiting condition that can arise up to 1 year AFTER delivery and present as transient HYPERthyroidism –> HYPOthyroidism or vice versa; majority become euthyroid after resolution
Postpartum Thyroiditis
A condition when thyroid is replaced by FIBROUS tissue and inflammatory infiltrate due to IgG-related systemic disease; presents with a hard, PAINLESS goiter
Riedel Thyroiditis
The most common cause of goiter (enlarged thyroid) worldwide, not in US
Iodine deficiency
Drugs that interfere with the normal function of the thyroid gland (can cause both hypo- and hyperthyroidism) and can cause goiter by stimulating TSH
Goitrogens
- Amiodarone
- Lithium
The most common cause of hypoparathyroidism with resultant hypocalcemia
Complication of thyroidectomy due to inadvertent injury or removal of the parathyroid glands.
Post-operation hypocalcemia can be treated using
Ca+2 and vitamin D supplements
Spasm/contraction of facial muscles upon tapping of facial nerve of cheek due to hypocalcemia
Chvostek sign
*STUDY AID: Chvostek for “Cheek”
Carpal spasms when brachial artery (triceps) is occluded with BP cuff
Trousseau sign (백조 손모양)
- STUDY AID: Trousseau sign for “Triceps”
Lab findings of hypocalcemia and hyperphosphatemia due to low parathyroid hormone
Primary Hypoparathryodism
Thymic and parathyroid hypoplasia in DiGeorge syndrome results from maldevelopment of ___ and ____ pharyngeal/branchial pouches
- 3rd (inferior PT and thymus)
- 4th (superior PT)
Hypocalcemia can cause
- (Hypertension/Hypotension)
- neuromuscular (hyperexcitability/hypoexcitability)
- Hypotension
- hyperexcitability
- STUDY AID:
1. think about ca+2 blockers
2. muscle spasm (chevostek sign))
A hereditary condition with hypocalcemia due to kidneys and bones NOT responding to the actions of PTH; presents with short stature, round face, developmental delay
Pseudohypoparathyroidism (type 1 A)
Bone abnormality seen in Pseudohypoparathyroidism; aka. Albright Hereditary Osteodystrophy
shortened 4th/5th fingers
Lab findings of Pseudohypoparathyroidism
PTH, Ca+2, Phosphate
↑ PTH
↓ calcium
↑ phosphate
Mutation of what gene is responsible for causing Pseudohypoparathyroidism?
GNAS gene
A hereditary condition that has same physical findings as in Pseudohypoparathyroidism but has COMPLETELY NORMAL lab findings; caused by GNAS gene mutation WITHOUT end-organ resistance to PTH
Pseudopseudohypoparathyroidism
Lab findings of Pseudopseudohypoparathyroidism
PTH, Ca+2, Phosphate
ALL NORMAL!
Lab findings of hypercalcemia, hypercalciuria, hypophosphatemia, and high parathyroid hormone; usually due to parathyroid adenoma or hyperplasia
Primary Hyperparathyroidism
↑ bone resorption in Primary Hyperparathyroidism increases the risk of what bone disorder?
Osteoporosis
PULSATILE administration of _______ induces a greater ↑ in osteoblast activity in proportion to osteoclast activity and a net ↑ in bone formation; used as a tx for osteoporosis
Recombinant PTH analog (Teriparatide)
Clinical features/signs of hypercalcemia due to primary hyperparathyroidism
*STUDY AID: “stones, thrones, bones, groans, and psychiatric overtones”
- Stones: renal stones due to hypercalciuria
- Thrones: polyuria
- Bones: bone pain
- Groans: constipation
- Psychiatric Overtones: confusion, depression, memory loss, etc.
Cystic bone spaces filled with BROWN fibrous tissue causing bone pain in primary hyperparthyrodism due to increased bone turnover
Osteitis Fibrosa Cystica
Osteitis Fibrosa Cystica consists of osteoclasts and deposition of
hemosiderin (a protein that stores iron)
- why it looks brown
A disorder caused by defective Ca-sensing receptors in the parathyroid gland and kidneys which leads to excessive renal Ca+2 reabsorption –> Hypercalcemia, HYPOcalciuria, and normal/↑ PTH
Familial Hypocalciuric Hypercalcemia
Why is PTH level normal or ↑ in Familial Hypocalciuric Hypercalcemia?
Because it requires HIGHER than normal calcium level to suppress PTH
- body increases PTH thinking Ca+2 is not enough until it can finally sense with higher than normal Ca+2 level
Diuretic drug that can cause hypercalcaemia by ↑ the DCT reabsorption of Ca2+; lab findings include hypercalcemia and low PTH
Thiazides
↑ PTH due to ↓ Ca+2 absorption and/or ↑ phosphate level; most often caused by “chronic kidney disease” (can’t activate vitamin D, can’t reabsorb Ca+2 in kidney, and can’t excrete phosphate in kidney)
Secondary Hyperparathyroidism
- look for signs of CKD (↑ serum creatine or ↑ ALP)
Lab findings of Secondary Hyperparathyroidism
PTH, Ca+2, Phosphate
↑ PTH
↓ calcium
↑ phosphate
Autonomous overproduction of PTH due to chronic kidney disease (end-stage), leading to ↑Ca+2
Tertiary Hyperparathyroidism
Lab findings of Tertiary Hyperparathyroidism
PTH, Ca+2
↑↑ PTH
↑ calcium
What enzyme converts T4 into T3 (active) and rT3 (inactive) forms?
5’-Deiodinase
Shortened relaxation of deep tendon reflexes will be seen in (hypo/hyperthyroidism)
Hyperthyroidism
*STUDY AID: high thyroid hormone level –> increase BMR –> shortened reflex
Delayed relaxation of deep tendon reflexes will be seen in (hypo/hyperthyroidism)
Hypothyroidism
*STUDY AID: low thyroid hormone level –> decrease BMR –> delayed reflex
The thyroid-stimulating antibody of Graves disease is what kind of immunoglobuin?
IgG
Poor weight gain and stridor (due to compressive goiter) are serious neonatal manifestations of (hypothyroidsm/hyperthyroidism) seen in untreated maternal disease
Hyperthyroidism
- Neonatal Thyrotoxicosis due to untreated maternal Graves disease/hyperthyrodism
T4 and T3 are (steroid/peptide) hormones
Steroid
- can cross the placenta
TSH is a (steroid/peptide) hormone
peptide
ECG abnormality most likely seen in hypocalcemia
Prolonged QT
How does CKD affect vitamin D, Ca+2, and phosphate levels?
- Vitamin D: decreased active form –> ↓Ca+2 absorption from gut –> Hypocalcemia
- ↓ Ca+2 reabsorption in kidney –> Hypocalcemia
- ↓ Phosphate excretion in kidney –> Hyperphosphatemia
The site of PTH production and secretion
Parathyroid CHIEF cells
Tx that uses iodine-131, a radioactive element that emits beta rays, to destroy thyroid tissue.; used for Graves disease
RADIOACTIVE iodine ablation
Tx used for the IMMEDIATE control of symptoms in patients with hyperthyroidism/thyroid storm
Non-selective beta blocker (propranolol)
The transmembrane carrier/receptor that transports both iodine (both radioactive iodine or natural iodine) and Na+ into thyroid tissue
NIS (sodium/iodide symporter)
Elevated serum _____ indicates increased bone turnover in hyperparathyroidism
ALK (alkaline phosphatase)
Cytokine secreted by osteoblast when induced by PTH to activate osteoclasts –> increase serum calcium
IL-1
Enzyme that assists the chemical reaction that adds iodine to a protein called thyroglobulin, a critical step in GENERATING thyroid hormones
Thyroid Peroxidase (TPO)
The sites (2) of hypothalamus that produce ADH and oxytocin
Supraoptic nucleus (SON) & Paraventricular nucleus (PVN) of hypothalamus
Carrier proteins that carry Oxytocin and ADH from hypothalamus to posterior pituitary
Neurophysins
Characterized by low serum Na+ and osmolality, inappropriately concentrated urine, and clinically normal volume status (euvolemic hyponatremia)
SIADH
Characterized by intense thirst and polyuria with inability to concentrate urine due to LACK of ADH; caused by injury to hypothalamus (permanent) or posterior pituitary (transient)
Central Diabetes Insipidus
Tx for Central DI
Desmopressin
- urine osmolality will increase to normal level for central DI
Characterized by intense thirst and polyuria with inability to concentrate urine due to failure of response to ADH; caused by ADH receptor mutation or medications (lithium)
Nephrogenic Diabetes Insipidus
Tx for nephrogenic DI
Thiazide
*diuretic but produces a paradoxical antidiuretic effect in nephrogenic DI
Characterized by excessive intake of water, leading to hyponatraemia and polyuria; water restriction concentrates urine osmolality
1° (Psychogenic) polydipsia
The most common hormone produced by pituitary adenomas; causes hypogonadism in males & amenorrhea and galactorrhoea in females
Prolactin
- prolactinoma
Ocular defect due to compression of optic chiasm by pituitary adenoma; decreased peripheral vision
Bitemporal Hemianopsia
Prolactin (increases/suppresses) GnRH, leading to ____ LH & FSH
suppresses; decreased
Prolactin can cause ↓ GnRH, leading to ↓_____ production —> ↑ risk of osteoporosis and vaginal dryness & atrophy
Estrogen
Tx for prolactinoma
DA agonists
- Bromocriptine
- Cabergoline
Hypercortisolism caused by ACTH-secreting pituitary adenoma, ectopic ACTH production, or exogenous corticosteroids; presents with stretch marks and central obesity
Cushing syndrome
A Cushing syndrome caused by ACTH-secreting pituitary adenoma
Cushing disease
How do you distinguish Cushing syndrome caused by Cushing disease (pituitary adenoma) vs. ectopic ACTH secretion (SCLC)
ACTH and cortisol levels will be suppressed with HIGH-dose dexamethasone in Cushing Disease
- ACTH and cortisol will remain elevated in ectopic ACTH secretion
How do you distinguish Cushing syndrome caused by exogenous corticosteroids from other causes?
Low ACTH and atrophy of bilateral adrenal cortex
Hormones produced by Zonular Glomerulosa, Fasciculata, and Reticularis of adrenal cortex
- Aldosterone
- Cortisol
- Androgens
*STUDY AID: GFR
Destruction of adrenal glands due to autoimmune disease, leading to suppressed mineralocorticoids and glucocorticoids & increased ACTH production from the pituitary gland; presents with hypotension, hyperpigmentation, weight loss, and hypoandrogenism (lack of pubic hair)
Primary Adrenal Insufficiency
aka. Addison Disease
Why does Addison disease present with weight loss?
lack of cortisol production
What causes hyperpigmentation in Primary adrenal insufficiency (PAI)?
Increased ACTH (due to low cortisol and low aldosterone) which also induces melanin synthesis
Atrophy of adrenal glands due to chronic corticosteroid therapy, leading to suppressed ACTH & CRH production; presents WITHOUT hyperpigmentation since no ACTH production; aldosterone production is not affected
Secondary Adrenal Insufficiency
The most common cause of secondary AI
Glucocorticoid therapy
A medical emergency (fever, shock, mental status changes) caused by a lack of cortisol in patients with adrenal insufficiency; triggered by stress
Adrenal Crisis
A condition that decreases “CRH” (and therefore ACTH and cortisol) production due to sudden discontinuation of chronic STEROID therapy; aldosterone is NOT affected!
Tertiary Adrenal Insufficiency
Increased secretion of aldosterone from adrenal gland due to adrenal adenoma or hyperplasia; presents with low renin, hypokalemia, metabolic alkalosis, and treatment-RESISTANT hypertension
Primary Hyperaldosteronism
aka. Conn Syndrome
Evasion of edema and Na+ retention in primary Hyperaldosteronism due to secretion of ANP and natriuresis as compensatory mechanism
Aldosterone Escape
Admin of metyrapone will cause a ↓ in cortisol synthesis via inhib of 11-β-hydroxylase. In pts w/ an intact HPA axis, this will cause a reactive ↑ in ACTH, 11-deoxycortisol, and urinary 17-hydroxycorticosteroid lvls.
Congenital Adrenal Hyperplasia
A term to describe a triad that may indicate the presence of an insulinoma
- low blood glucose
- hypoglycemia symptoms (syncope, lethargy, diplopia)
- abrupt resolution of symptoms after normal glucose level
Whipple Triad
What is produced by an insulinoma in addition to insulin that distinguishes it from exogenous insulin use?
C-peptide
Tx for insulinoma
surgical resection/removal
Tumor of pancreatic a cells that overproduces glucagon, leading to hyperglycemia, diarrhea, weight loss (lipolysis) and dermatitis (necrolytic migratory erythema)
Glucagonoma
Tx for Glucagonoma
Octreotide (for diarrhea) & surgical resection
Tumor of pancreatic D cells that overproduces somatostatin, leading to inhibition of other hormone secretion (insulin, glucagon, secretin, and cholecystokinin); presents with diabetes/glucose intolerance, steatorrhea (fatty stool), and gallstones
Somatostainoma
A hormone released into the bloodstream by the duodenum to inhibit the gastric acid secretion & stimulate the bicarbonate secretion
Secretin
A hormone which is secreted by cells in the duodenum and stimulates the release of BILE into the intestine
Cholecystokinin
Tx for Somatostainoma
Octreotide (somatostatin analog) & Surgical resection
Tumor of pancreatic cells that overproduces VIP, leading to watery diarrhea (tea-colored, persistent even with fasting), achlorhydia, and hypokalemia
VIPoma
Tx for VIPoma
Octreotide (somatostatin analog) & Surgical resection
Tumor of neuroendocrine cells from GI (terminal ileum) that produces ↑ 5-HT (serotonin), leading to recurrent diarrhea, wheezing, flushing/reddening, RIGHT-sided valvular heart disease, and niacin deficiency (pellagra)
- remember that serotonin and niacin are both derived from tryptophan!
Carcinoid Tumor
Since Carcinoid tumor arises from NEUROENDOCRINE cells, it is + for what IHC stains?
- think about SCLC!
- Chromogranin A
- Synaptophysin
- Neuron-specific enloase
Tx for Carcinoid tumor
Octreotide (somatostatin analog) & Surgical resection
The chance that carcinoid tumor can metastasize, present with 2nd malignancy, and are multiple
All 1/3
- rule of thirds!
Caused by any drug that ↑ 5-HT, leading to ↑ neuromuscular activity (hyperreflexia, hypertonia, seizure), autonomic instability (diarrhea, diaphoresis, hyperthemia), and altered mental status
Serotonin syndrome
In order to avoid Serotonin syndrome, what is required after discontinuing a MAOI and before initiating SSRI therapy?
2 week washout period to allow time for monoamine oxidase (MAO) regeneration
Tx for serotonin syndrome
Cyproheptadine (5-HT receptor antagonist)
MEN 1 are associated with what three tumors?
- Pituitary tumor
- Pancreatic tumor
- Parathyroid tumor
- 3 P’s
MEN 2A are associated with what three tumors?
- Parathyroid tumor
- Pheochromocytoma
- Medullary Thyroid Carcinoma
- 2 P’s
MEN 2B are associated with what three tumors?
- Pheochromocytoma
- Medullary Thyroid Carcinoma
- Marfanoid habitus/Mucosal Neuroma (oral/GI neuroma)
- 1 P
Mutation associated with MEN 1
MEN1 (menin, tumor suppressor gene)
Mutation associated with MEN 2A/2B
RET (oncogene, codes for tyrosine kinase)
Inheritance pattern for all MEN syndromes
Dominant
- STUDY AID: “all MEN are dominant”
A neuroendocrine tumor arising from the chromaffin cells of the Adrenal Medulla characterized by excess production of catecholamines; presents with HTN, diaphoresis, and palpitations.
Pheochromocytoma
Since Pheochromocytoma arise from NEUROENDOCRINE (chromaffin) cells, it is + for what IHC stains?
- Chromogranin A
- Synaptophysin
- Neuron-specific enloase
Adrenal medulla (chromaffin cells) arises from
Neural crest cells (ectoderm layer)
Adrenal cortex arises from
Mesoderm
A drug that decreases cortisol production by inhibiting 11ß hydroxylase
Metyrapone
What lab change is expected in PRIMARY adrenal insufficiency after Metyrapone administration??
↑ ACTH
↑ 11-deoxycortisol (cortisol precursor)
What lab change is expected in Secondary adrenal insufficiency after Metyrapone administration??
↓ ACTH
↓ CRH
↓ 11-deoxycortisol (cortisol precursor)
*both fail to rise since chronic steroid use ↓ the body’s ability to produce corticosteroids
Blistering rashes/dermatitis that can occur with too much glucagon in glucagonoma
Necrolytic Migratory Erythema
What is a metabolite of serotonin (5-HT); elevated in carcinoid tumor
5-hydroxyindoleacetic acid (5-HIAA)
The most likely organ that carcinoid tumor will metastasize
Liver
What unique heart presentation is associated with carcinoid tumor due to increased serotonin?
Right-sided heart valvular disease (tricuspid, pulmonic valves)
Production of what adrenal hormone remains intact in secondary (corticosteroid-therapy) AI?
Aldosterone (mineralcorticoids)
- zona glomerulosa is not affected by “secondary” AI
All congenital adrenal “enzyme” deficiencies are what inheritance pattern?
AR
Why does Congenital Adrenal Hyperplasia present with BILATERAL adrenal gland enlargement and hyperpigmentation?
due to ↑ ACTH stimulation on adrenal glands and (MSH) Melanocyte-stimulating hormone
What CAH enzyme deficiency causes ↓ mineralocorticoids, ↓ glucocorticoids, and ↑ androgens –> hyponatremia, hypotension, hyperkalemia, and ambiguous genitalia (only in females) or precocious puberty (in males)
21-hydroxylase
↑ _____ confirms the diagnosis of 21-hydroxylase deficiency
17-hydroxyprogesterone
What CAH enzyme deficiency causes ↓ aldosterone, ↓ glucocorticoids, and ↑ androgens –> HYPERtension and hypokalemia, and ambiguous genitalia (only in females) or precocious puberty (in males)
11β-hydroxylase
Why does 11β-hydroxylase deficiency lead to HYPERtension and hypokalemia despite decreased aldosterone production?
due to ↑ 11-deoxycortisol that acts as mineralocorticoids
What CAH enzyme deficiency causes ↑ mineralocorticoids, ↓ glucocorticoids, and ↓ androgens –> Hypertension, hypokalemia, and hypogonadism (boys appear phenotypically female)
17α-hydroxylase
Tx for CAH
Corticosteroids
Diabetes Mellitus present with what 3 P’s as clinical symptoms/signs?
- Polyuria
- Polydipsia
- Polyphagia
Diabetes Mellitus Type 1 is caused by autoimmune T-cell mediated destruction of
“B” cells of pancreas islet cells
4 types of antibodies found in DM1
- Islet Cell Antibodies (ICA)
- Glutamic Acid Decarboxylase (GAD) antibodies
- Insulin Autoantibodies (IAA)
- Protein Tyrosine Phosphatase (PTP) antibodies
Human MHC (HLA) associated with DM1
HLA-DR4
HLA-DR3
- STUDY AID: 4-3 is “type 1”
Diabetes Mellitus Type 2 is caused by increased resistance to ____ and “progressive” pancreatic B-cell failure
Insulin
Which DM is associated with obesity?
Type 2
Which DM is associated with strong genetic predisposition?
Type 2
- Type 1 is associated with HLA but has weak genetic predisposition
Which DM shows histological finding of pancreatic islet AMYLOID deposition
Type 2
- It’s suggested that progressive beta-cell failure in type 2 diabetes correlates with the formation of pancreatic islet amyloid deposits
Which DM shows histological finding of pancreatic islet LEUKOCYTE infiltration
Type 1
Cleavage of proinsulin in pancreatic β-cell secretory granules yields insulin and what other protein?
C-peptide
- also amylin
Insulin is (steroid/peptide) hormone
Peptide
Circulating levels of _____ can be used as a marker of endogenous insulin secretion
C-peptide
Fasting Plasma Glucose level to diagnose diabetes
≥ 126 mg/dL
- STUDY AID: think of my maximum weight!
HbA1c level to diagnose diabetes
≥ 6.5%
2-hour oral glucose tolerance test level to diagnose diabetes
≥ 200 mg/dL
The most effective tx intervention in patients with diabetes
Smoking cessation (if smoking)
HbA1c level reflects average blood glucose over prior ___ months
3
HbA1c assay uses the life span of circulating ____ to measure blood glucose
erythrocytes
*RBCs live about 3 months
A group of hormones that is released from enteroendocrine cells of GI after eating and augment the secretion of insulin from pancreatic beta cells
Incretins
- Glucose-dependent Insulinotropic Polypeptide (GIP)
- Glucagon Like Peptide-1 (GLP-1)
Does ↑ blood glucose level induce the release of incretins?
NO
- Incretins are secreted only after consumption of food (glucose)!
The most common complication of disease in diabetic patients
Coronary Artery Disease
Insulin resistance in DM2 is caused by phosphorylation of ____ by serine kinase
insulin receptor substrate (IRS)
Insulin is cleared by what two organs?
Renal and Liver
A condition caused by increased ketone production due to insulin noncompliance or increased insulin requirement in diabetic patients; presents with delirium, Kussmaul breathing, abdominal pain/nausea/vomiting, and dehydration
Diabetic Ketoacidosis (DKA)
- STUDY AID: “DKA is Deadly”
- Delirium
- Kussmaul breathing
- Abdominal pain/nausea/vomiting
- Dehydration
Unique feature in diabetic ketoacidosis due to exhaled acetone from increased ketone production
Fruity breath
Tx for Diabetic Ketoacidosis (DKA)
- Normal Saline
- IV Regular insulin
- K+ (if < 3.3)
Why is K+ must be given in patients with Diabetic Ketoacidosis and K+ < 3.3?
Insulin activates Na+/K+ ATPase, so giving IV regular insulin will quickly drive potassium into cells, further lowering serum potassium level –> potentially can cause hypokalemia
A condition that often presents in elderly patients w/ type 2 DM with limited access to water –> hyperglycemia leading to osmotic diuresis –> polyuria –> increased serum osmolality and dehydration
Hyperosmolar Hyperglycemic State (HHS)
How do you distinguish Hyperosmolar Hyperglycemic State (HHS) from Diabetic Ketoacidosis (DKA)?
HHS: some insulin is still present, so ketones are ABSENT (no fruity breath)
Tx for Hyperosmolar Hyperglycemic State (HHS)
- Normal Saline
- IV Short Acting (regular) insulin
- K+ (if < 3.3)
- same as DKA
Tumor of pancreatic b cells that overproduces insulin, leading to whipple’s triad
Insulinoma
