Endocrine Flashcards
(69 cards)
1
Q
Congenital hypothyroidism
A
Decreased T4 levels
- Endemic Cretinism= insufficient iodine in utero
- Sporadic= defect in T4 formation in utero, developmental thyroid formation failure
Symptoms:
- Lethargy, poor feeding
- Jaundice, macroglossia
- Constipation, umbilical hernia, myxedema
- Muscle hypotonia, hoarse cry
- ASD, VSD
Pot bellied, Pale, Puffy-faced child with Protruding umbilicus, protuberant tongue
2
Q
Somatomedin C
A
AKA IGF-1= insulin-like growth factor 1
- GH Secreted by pituitary–> liver produces IGF-1
- induces chondrocytes to proliferate along epiphyseal plate (long bone growth!)
3
Q
Fetal adrenal gland
A
Outer zone= adult zone
- No function until late in gestation: begins secreting cortisol
- Controlled by ACTH and CRH from fetal pituitary and placenta
- Cortisol–> fetal lung maturation and surfactant secretion
Inner zone= Active fetal zone
- Produces androgens with placenta
- Lacks 3-beta-hydroxysteroid to convert pregnolone–> progesterone
4
Q
Anterior pituitary
A
Secretes FSH, LH, ACTH, TSH, prolactin, GH, MSH
- Derived from oral ectoderm (Rathke’s pouch–> craniopharyngioma) vs posterior pituitary= neuroectoderm
- Alpha subunit= TSH, LH, FSH, hCG common subunit
- Beta subunit= hormone-specific
5
Q
GLUT-1 receptors
A
Insulin INDEPENDENT
- RBCs, Brain
6
Q
GLUT-2 receptors
A
Bidirectional
- Beta-islet cells
- Liver, kidney, small intestine (insulin-independent uptake)
7
Q
GLUT-4 receptors
A
Insulin DEPENDENT
- Adipose tissue
- Skeletal muscle
8
Q
Insulin release
A
Beta cells in pancreas: center of islet
- GLUT-2 transporter brings in glucose
- Glycolysis in Beta cell–> ATP/ADP ratio increase
- ATP binds and closes K+ channels
- Membrane depolarizes
- Ca+2 influx into beta cell
- Exocytosis of insulin granules
9
Q
Glucagon release
A
Alpha-cells in pancreas: periphery of islet
Secreted in response to:
- Hypoglycemia
- Increased serum [amino acids]
- Adrenergic stimulation (epi–> alpha2 receptors)
- CCK
- Ach
Inhibited by:
- Insulin
- Hyperglycemia
- Somatostatin
10
Q
17-alpha-hydroxylase deficiency
A
Hypertension, hypokalemia
Males: decreased DHT–> pseudohermaphroditism (ambiguous genitalia, undescended testes
Females: internally and externally phenotypic female lacking secondary sex characteristics
**Enlarged adrenal glands d/t increased ACTH
11
Q
21-hydroxylase deficiency
A
HYPOtension, hyperkalemia, increased renin activity, volume depletion
Females: masculinization; pseudohermaphroditism
**Enlarged adrenal glands d/t increased ACTH
12
Q
11-beta-hydroxylase deficiency
A
HYPERtension:
- increased 11-deoxycorticosterone= mineralocorticoid, secreted in excess (HTN)
- Decreased aldosterone
Females: Masculinization
**Enlarged adrenal glands d/t increased ACTH
13
Q
Growth Hormone
A
Anterior pituitary
Stimulates linear growth:
- increases liver IGF-1/somatomedin C secretion–> - induces chondrocytes to proliferate along epiphyseal plate (long bone growth)
Increased secretion in exercise, sleep
- Inhibited by glucose, somatostatin
14
Q
Cortisol
A
Adrenal zona fasciculata, bound to corticosteroid-binding globulin (CBG)
- Maintains BP (upregulates alpha1 receptors on arterioles–> increased sensitivity to NE, epi
- Decreases bone formation
- Anti-inflammatory/immune suppressive (blocks IL-2, etc)
- Increased insulin resistance
- Increased gluconeogenesis, lipolysis, proteolysis
- Inhibits fibroblasts–> striae
15
Q
PTH
A
Secreted by chief cells in parathyroid
Regulated by:
- depleted Ca+2–> increased PTH
- Decreased Mg+2–> increased PTH
- Absent Mg+2–> decreased PTH (needs Mg+2 for manufacuring in chief cells); can be caused by diarrhea, aminoglycosides, diuretics, alcohol abuse
MOA:
- Stimulates cAMP–> increased osteoblastic RANK-L + M-CSF expression–> increased osteoclast activity
- Decreases osteoprotegerin release (OPG= inhibitor at RANK-L)
16
Q
cAMP signaling hormones (Gs/Gi)
A
Releasing hormones: FSH LH--> leydig (testosterone)/ Corpus luteum (progesterone) SCT TSH CRH hCG ADH (V2 receptor) MSH PTH Calcitonin GHRH Glucagon
17
Q
cGMP signaling hormones
A
Vasodilators:
ANP NO (endothelial derived relaxing factor)
18
Q
IP3 signaling hormones (Gq)
A
GnRH GHRH Oxytocin ADH TRH Histamine (H1) Angiotensin II Gastrin
19
Q
Steroid receptor
A
Vitamin D Estrogen Testosterone T3/T4 Cortisol Aldosterone Progesterone
20
Q
Intrinsic tyrosine kinase
A
Growth factors:
Insulin IGF-1 FGF PDGF EGF
21
Q
Receptor-associated tyrosine kinase (JAK/STAT)
A
Prolactin
Immunomodulators (cytokines, IL-2,6,8, IFN)
GH
22
Q
Sex hormone binding globulin (SHBG)
A
Binds sex hormones:
Men: increased SHBG–> decreased free T–> gynecomastia
Women: decreased SHBG–> increased free T–> hirsutism
- SHBG increased in pregnancy
23
Q
Thyroid hormone function
A
- bone growth (synergism with GH)
- CNS maturation
- increases B1 receptors in heart
- increases BMR (basal metabolic rate)
- increases glycogenolysis, gluconeogenesis, lipolysis
24
Q
Thyroid hormone production
A
- Iodine (I-) uptaken from blood by follicular cell
- TPO (Thyroid Peroxidase) oxidizes I- –> I2
- Follicular cell secretes I2, thyroglobulin into lumen (colloid)–> MIT/DIT
- Peroxidase (TPO) in lumen couples MIT/DIT–> T3/T4
- T3/T4 re-imported into follicular cell–> proteolysis–> released into blood (bound to TBG= thyroid binding globulin)
- TBG increased by estrogen, decreased by liver failure
- T4= major product; converted by 5’-deiodinase in periphery to active T3
25
Wolff-Chaikoff effect
Excess iodine temporarily inhibits TPO
(thyroid peroxidase)
--> decreased iodine organification
--> Decreased T3/T4 production
26
Propylthiouracil
PTU
MOA:
- blocks TPO formation of T3/T4
- Blocks 5'deiodinase conversion of T4--> T3
Tox: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity
27
Methimazole
MMI
MOA; blocks TPO formation of T3/T4
Tox: skin rash, agranulocytosis, aplastic anemia, teratogen?
28
Dexamethasone suppression test
Normal function: cortisol suppressed by low dexamethasone
ACTH-pituitary tumor (Cushing's): suppressed by high dexamethasone
- Also can take venous sample of petrosal sinus
- 24 hour urine collection: free cortisol 3x upper limit of normal
Ectopic ACTH-producing tumor (SCLC, bronchial carcinoids)/ Cortisol-producing tumor (adrenal adenoma): remains elevated with high dose dexamethasone
29
Conn's syndrome
Aldosterone-secreting adrenal adenoma
- Hypertension, Hypokalemia (like 17-alpha-hydroxylase deficiency)
- Metabolic alkalosis
- low plasma renin
Symptoms:
- HTN
- Weakness, paresthesias (hypoklemia)
Bilateral or unilateral
Treatment:
- Surgery to remove tumor
- Spironolactone (aldosterone antagonist)
30
Secondary hyperaldosteronism
Low perfusion in kidney (d/t renal artery stenosis, chronic renal failure, CHF, cirrhosis, nephrotic syndrome)
--> increased renin production
Treatment:
- Spironolactone
31
Addison's disease
Chronic primary adrenal insufficiency
- Adrenal atrophy/destruction of adrenals (autoimmune- increased risk with T1DM, TB, metastasis)
Deficiency of aldosterone, cortisol
- Hypotension (hyponatremic volume contraction)
- Hyperkalemia
- Acidosis
- Skin hyperpigmentation (MSH: increased ACTH--> MSH increase from POMC)
Treatment: Corticosteroids
32
Secondary adrenal insufficiency
Decreased pituitary ACTH
- No skin hyperpigmentation
- no hyperkalemia
Tx: responds to ACTH
33
Pheochromocytoma
Tumor of adrenal medulla in ADULTS
- Chromaffin cell (neural crest)
Secretes epi, NE, DA--> episodic HTN
Labs:
- Increased urinary VMA (breakdown product of NE, epi)
- Increased plasma catecholamines
Associated with:
- NF-1
- MEN 2A, 2B
Treatment:
- Alpha-antagonist (irreversible): pheoxybenzamine (avoid hypertensive crisis)
- Beta blocker: slow HR
- Surgical removal
rule of 10s (10%): malignant, bilateral, extra-adrenal, calcify, kids
34
Neuroblastoma
MOST Common Tumor of adrenal medulla in children
Presentation:
- Opsoclonus-myoclonus syndrome= non-rhythmic conjugate eye movements + myoclonus
- Retroperitoneal mass, anorexia, weight loss
- Less likely to see HTN
- elevated HVA in urine (catecholamines)
Histo:
- Solid sheets of small blue round cells
- Can occur anywhere along sympathetic chain
**Overexpression of N-myc--> rapid tumor progression (transcription factor)
35
Hashimoto's thyroiditis
anti-TPO, antithyroglobulin antibodies
- HLA-DR5
- Increased risk of non-Hodgkin's lymphoma
- Normal ESR
- Chronic, progressive
Histo:
- Hurthle cells
- Lymphocytic infiltrate with germinal centers
- Enlarged, nontender thyroid
36
Subacute thyroiditis (de Quervain's)
Self-limited hypothyroidism after flu-like illness
Histo: granulomatous inflammation
- Neutrophils: lymphocytes, histiocytes, multi-nucleated giant cells (granuloma)
- disrupted follicles around collioid
Findings:
- Increased ESR, jaw pain, early inflammation, tender thyroid
- Thyrotoxic--> hypothyroid--> euthyroid
Tx: NSAIDs for pain
37
Riedel's thyroiditis
Thyroid replaced by fibrous tissue (hypothyroid)
Findings:
- Fixed, hard (rock-like) painless goiter
- May extend into surrounding tissue
* * Manifestation of IgG4-related systemic disease (autoimmune pancreatitis)
38
Hypothyroid myopathy
Pale muscle fibers with:
- decreased striation
- deposition of mucinous material
- atrophy of Type II mucle fibers
Symptoms:
- Weakness
- Fatiguability
- Muscle pain, cramping
39
Toxic multinodular goiter
Focal patches of hyperfunctioning follicular cells
- Work independently of TSH (mutation in TSH receptor)
- Increased release of T3, T4
Jod-Basedow phenomenon= thyrotoxicosis after repletion of iodine deficency
40
Grave's disease
Diffusely enlarged goiter secreting TSI (thyroid-stimulating immunoglobulins)--> autoimmune hyperthyroidism
- Proptosis (opthalmopathy, EOM swelling)
- Pretibial myxedema
- Increase in connective tissue deposition
Stress-induced (Childbirth)
41
Thyroid Storm
Thyrotoxicosis:
- Stress-induced catecholamine surge--> death by arrhythmia
- Serious complication of Grave's, hyperthyroid disorders
Increased ALP d/t increased bone turnover
Tx:
- Glucocorticoids for exopthalmos
- Beta-blockers for relief of sympathetic activation
- Block iodine organification (Iodide salts, Propylthiouracil, Methimazole)
- Radioactive iodine (ablate thyroid with I-131)
42
Primary hyperparathyroidism
Adenoma--> Hypercalcemia
- Hypercaluria, hypophosphatemia
- Increased PTH, alk phos, cAMP in urine
- Weakness, constipation
Osteitis fibrosa cystica= cystic bone spaces with brown fibrous tissue (bone pain)
43
Secondary hyperparathyroidism
Decreased gut Ca+2 absorption, increased phosphate
- Chronic renal disease (hypovitaminosis D--> decreased Ca+2 absorption)
Hypocalcemia, hyperphosphatemia in chronic renal failure (decreased phosphate in other causes)
- Increased alk phos, PTH
Renal osteodystrophy= bone lesions d/t secondary/tertiary hyperpara
44
Tertiary hyperparathyroidism
Refractory (autonomous) hyperparathyroidism d/t chronic renal disease
VERY elevated PTH, elevated Ca+2
45
Albright's hereditary osteodystrophy
AD: kidney unresponsive to PTH
- -> hypocalcemia,
- shortened 4th/5th digits
- short stature
- Resistance to TSH, LH, FSH (all stimulate Gs alpha pathway)
46
Acromegaly
Pituitary adenoma--> excess GH
- Large tongue, deep furrows
- Deep voice
- Large hands, feet, coarse faces
- Impaired glucose tolerance
Diagnosis:
- Increased serum IGF-1
- fail to suppress serum GH after oral glucose tolerance test
Tx: resect adenoma, somatostatin analog if not cured
47
Causes of diabetes insipidus
```
Central: lack ADH
- Pituitary tumor
- Trauma
- Surgery
- Langerhans cell Histiocytosis
Treatment: intranasal Desmopressin
```
Nephrogenic= kidney doesn't respond to ADH
- hereditary
- secondary to hypercalcemia
- Lithium
- Demeclocyline (ADH antagonist)
Treatment: HCTZ, indomethacin (NSAID), amiloride
48
SIADH
Causes:
- Ectopic ADH (SCLC)
- CNS/head trauma
- Pulmonary disease
- Drugs (cyclophosphamide)
```
Treatments:
Fluid restriction
IV saline
Conivaptan
Tolvaptan
Demeclocycline
```
49
Maternal diabetes
Insulin must be given to control blood glucose (insulin does not cross placenta)
Poor control
- Hypoglycemia of newborn (beta islet cell hyperplasia due to excess glucose exposure in utero)
- Caudal regression syndrome (sacral agenesis--> lower extremity paralysis, urinary incontinence)
- Transposition of the great vessels
50
Glucagonoma
Pancreatic tumor (rare)
Presentation:
- Migratory erythema
- Hyperglycemia (diabetes)
- Stomatitis, chelosis
- Abdominal pain
51
VIPoma
Pancreatic tumor
Presentation:
- Diarrhea
- Metabolic acidosis
- Hypokalemia
52
Somatostatinoma
Pancreatic delta cell tumor
Presentation:
- Abdominal pain
- Gallstones
- Constipation
- Steatorrhea
Labs:
- Decreased insulin, glucagon, CCK, secretins
- Decreased gastric motility
53
Carcinoid syndrome
Carcinoid tumor= neuroendocrine cells
- Metastatic small bowel tumor secreting 5-HT (most common tumor of appendix)
- Only seen if tumor metastasizes from bowel (5-HT digested in liver)
Symptoms:
- Recurrent diarrhea
- Cutaneous flushing
- Asthmatic wheezing
- Right-sided valvular disease
- Increased serotonin in urine
- Niacin deficiency
Treatment: Somatostatin analog (octreotide)
54
MEN 1
Werner's syndrome: Autosomal Dominant
DIAMOND; 3Ps
- Pituitary tumor
- Parathyroid tumors
- Pancreatic endocrine tumors (Zollinger-Ellison, insulinoma, VIPoma, glucagonoma)
Presentation: kidney stones, stomach ulcers
55
MEN 2A
Sipple's syndrome: Autosomal Dominant
SQUARE: 2 Ps
- Parathyroid tumors: 3rd/4th pharyngeal pouch
- Pheochromocytoma
- Medullary thyroid carcinoma (calcitonin): 4th/5th pharyngeal pouch
** ret gene mutation (tyrosine kinase)
56
MEN 2B
Autosomal dominant
TRIANGLE: 1 P
- Oral/intestinal ganglioneuromatosis (marfanoid habitus)
- Medullary thyroid carcinoma (calcitonin)
- Pheochromocytoma
** ret gene mutation (tyrosine kinase)
57
Metformin
Biguanide
MOA: unknown;
- decreases gluconeogensis
- increases glycolysis, peripheral glucos uptake
Oral: 1st line in T2DM
Tox:
- GI upset
- Lactic acidosis (contraindicated in renal failure)
58
Tolbutamide, chlorpropamide
Sulfonylureas (1st generation)
MOA: close K+ channel in Beta cell membrane (like ATP)--> cell depolarizes--> Ca+2 influx--> insulin release
Only for T2DM
Tox: Disulfiram-like effects
59
Glyburide
Glimepiride
Glipizide
Sulfonylureas (2nd generation)
MOA: close K+ channel in Beta cell membrane (like ATP)--> cell depolarizes--> Ca+2 influx--> insulin release
Only for T2DM
Tos: hypoglycemia
60
Pioglitazone, Rosglitazone
Glitazones/thiazolidinediones
MOA: Binds PPAR-gamma nuclear transcription regulator--> increased insulin-responsive genes--> increased insulin sensitivity in peripheral tissue
Mono or combo in T2DM
Tox:
- Weight gain, edema, hepatotoxic, heart failure
61
Acarbose, miglitol
Alpha-glucosidase inhibitors
MOA: inhibit intestinal brush-border alpha-glucosidases--> delayed sugar hydrolysis, glucose absorption
Mono or combo in T2DM
Tox: GI disturbances
62
Pramlintide
Amylin analog
MOA: decreases glucagon
T1 and T2DM
TOx: hypoglycemia, nausea, diarrhea
63
Exenatide, Liraglutide
GLP-1 analogs
MOA: increased insulin, decreased glucagon release
T2DM
Tox: N/V, pancreatitis
64
Linagliptin
Saxagliptin
Sitagliptin
DPP-4 inhibitors
MOA: increased insulin, decreased glucagon release
T2DM
Tox: urinary, respiratory infections
65
Somatostatin
Octreotide
Use: acromegaly, carcinoid tumor
gastrinoma, glucagonoma, esophageal varices
66
Demeclocyline
Tetracycline, ADH antagonist
Use: SIADH
Tox:
- Nephrogenic DI
- Photosensitivity
- Abnormalities of bone, teeth
67
Basal insulin types
NPH (2 times/day)
| Glargine, Detemir (1x/day)
68
Post-prandial insulin
Regular: peaks 2-4 hours after administration
- use IV in DKA
Lispro, aspart, glulisine: peak 45 minutes after administration
- Use to prevent post-meal hyperglycemia
69
T2 Mature onset diabetes of the young (MODY)
Defect in Glucokinase enzyme (specific to liver, pancreatic beta-cells)- has high Km
- Can also have defect in transcription factors for insulin
