Endocrine Flashcards
What does the thyroglossal duct become?
What if it persists?
Normally thyroglossal duct –> foramen cecum
If it persists –> thyroglossal duct cyst
midline mass that moves with swallowing
What is the most common site of ectopic thyroid tissue?
The tongue
What adenohypophyseal hormones share a common subunit?
These all share the same alpha subunit (beta determines spec.)
TSH
LH
FSH
hCG
What do the basophil cells secrete in the anterior pituitary?
B-FLAT
Basophils: FSH LH ACTH TSH
What endocrine cell types are found in the pancreas?
Beta - Insulin
Alpha - Glucagon
Delta - Somatostatin
PP - Pancreatic polypeptide
This is the order of abundance
What tissues can take up glucose regardless of insulin status?
BRICK L
Brain RBC's Intestine Cornea Kidney Liver
What are the glucose transporters and their locations?
GLUT1 (insulin-independent) –> RBC’s & brain
GLUT2 (bidirectional) –> Beta cells, liver, kidney, small intestine
GLUT4 (insulin-dependent) –> Adipose tissue, skeletal muscle
What is insulin’s effect on renal tubules?
Causes sodium retention
What 3 things cause release of insulin?
What 3 things inhibit it?
Release:
Hyperglycemia
GH (causes insulin resistance –> increased release)
Beta2 agonists
Inhibit:
Hypoglycemia
Somatostatin
Alpha2 agonists
What are the steps within beta cells leading to insulin release?
Glucose enters via GLUT2 Glycolysis --> ^ATP ATP-sensitive K+ channels close --> Depolarization Voltage-gated Ca2+ channels open Exocytosis of insulin granules
What pathways are responsible for the intracellular effects of insulin?
Phosphoinositide-3 kinase pathway –> GLUT4 inserted into membrane & synthesis of glycogen, lipids, proteins
RAS/MAP kinase pathway –> Cell growth, DNA synthesis
What changes occur within target tissues that cause insulin resistance?
Serine kinase phosphorylation of signaling molecules. This causes inhibition of the Phosphoinositide-3 kinase pathway so that GLUT4 cannot be inserted into the membrane.
What is the regulation of prolactin?
TRH –> +Prolactin
Dopamine –> -Prolactin
What does CRH stimulate release of?
ACTH
Melanocyte-Stimulating Hormone (MSH)
Beta-endorphin
What is Somatostatin’s effect in the pituitary?
Decreases GH & TSH release
What are the effects of growth hormone?
Stimulates linear growth & muscle mass (IGF-1 mediated)
Insulin resistance
What can stimulate GH secretion?
Inhibit?
Stimulated by:
Pulsatile GHRH
Sleep
Exercise
Inhibited by:
Glucose
Somatostatin
How does 17-alpha-hydroxylase deficiency present?
Cortisol & androgens cannot be produced:
Hypertension
Males - pseudohermaphroditism (ambiguous genitalia)
Females - normal anatomy, no secondary sex characteristics
How does 21-alpha hydroxylase deficiency present?
Most common form of congenital adrenal hyperplasia
^Androgens, deficient cortisol & mineralocorticoids
Hypotension
Hyperkalemia
Masculinization in females –> pseudohermaphroditism
How does 11-beta-hydroxylase deficiency present?
^Androgens, ^mineralocorticoids, deficient cortisol
Hypertension (11-deoxycorticosterone)
Hypokalemia
Masculinization of females
What is seen with congenital aromatase deficiency?
Increased Testosterone and decreased Estrogen levels
Maternal hirsutism while pregnant w/ affected fetus
Female pseudohermaphroditism
What are the actions of cortisol?
BBIIG:
Bones/BP
Immunosuppression/Insulin resistance
Glucose production
Decreases bone formation
Upregulates alpha1 receptors on arterioles (sensitizes)
Anti-inflammatory
Diabetogenic
Gluconeogenesis, lipolysis, proteolysis, inhibits fibroblasts
How can one differentiate primary adrenal insufficiency vs HPA axis dysregulation?
Metyrapone test
Metyapone inhibits 11-beta-hydroxylase –> should see compensatory rise in ACTH –> Increased cortisol precursors (urinary 17-hydroxy-corticosteroids or 11-deoxycortisol)
If ACTH^ but not the precursors –> adrenal problem
If no ACTH^ –> HP axis problem
How does cortisol affect blood pressure?
1) It upregulates Alpha1 adrenergic receptors on arterioles –> sensitizes them to catecholamines
2) It increases transcription of phenylethanolamine-N-Methyltransferase (NE–>EPI)
How does PTH stimulate osteoclastic activity?
Increases production of M-CSF & RANK-L in osteoBLASTS
How is PTH secretion regulated?
Decreased serum Ca2+ –> ^PTH
Decreased serum Mg2+ –> PTH
Very low serum Mg2+ –> Decreased PTH
Thus, if magnesium levels are very low, a patient may not respond well to Calcium supplementation (need Mg2+ as well).
What can cause hypomagnesemia?
Diarrhea
Aminoglycosides
Diuretics
Alcohol abuse
What form of Vit. D is active?
What forms are inactive?
Active = 1,25-Cholecalciferol = Calcitriol Inactive = 25-OH-D3 & 24,25-OH-D3
How is Vit. D acquired?
Where is Vit. D activated?
D2 is dietary, D3 is synthesized in skin
Converted to 25-OH-D3 in liver
Converted to 1,25-OH-D3 in kidney PCT
What are the effects of Calcitriol?
^Bone resorption of calcium & phosphate
^GI absorption of calcium & phosphate
What hormones function through cAMP?
FLAT ChAMP
FSH LH ACTH TSH CRH hCG ADH (V2) MSH PTH
What hormones function through cGMP pathways?
The vasodilators:
NO (EDRF)
ANP
What hormones function through tyrosine kinase –> MAPK?
Growth factors: Insulin IGF-1 FGF PDGF EGF
What hormones function through a steroid receptor?
VETT CAP
Vit. D Estrogen Testosterone T3/T4 Cortisol Aldosterone Progesterone
What hormones function through tyrosine kinase –> JAK/STAT?
Acidophiles & cytokines:
Prolactin
GH
IL-2,IL-6,IL-8,IFN
What are the steroid hormones bound to in the circulation?
Testosterone/Estrogen - Sex Hormone Binding Globulin (SHBG)
Corticosteroids - Transcortin (CBG)
T3/T4 - Thyroxine Binding Globulin (TBG)
Aldosterone/Progesterone - Albumin, CBG
What is the function of T3?
4 B's: Brain maturation Bone growth Beta-adrenergic effects Basal metabolic rate
^Beta1 receptors in the heart –> ^CO,HR,SV,Contractility
^Na+/K+ ATPase activity –> ^BMR,RR,Temperature
^Glycogenolysis, gluconeogenesis, lipolysis
What maintains the high testosterone levels seen in the testes?
Androgen Binding Protein (ABP) secreted by Sertoli cells
What can change the levels of Thyroxine Binding Globulin (TBG)?
Liver failure –> decreased TBG
Pregnancy/OCP’s –> Increased TBG
What type of thyroid hormone is most active?
T3 is most active
T4 is the majority produced in thyroid
rT3 is not active at all
T4–>T3 in periphery via 5-deiodinase
What is the Wolff-Choikoff effect?
Excess iodine inhibits Thyroid Peroxidase (TPO) temporarily –> decreased organification of iodine –> decreased T3/T4
Can be used if radioactive iodide is accidentally ingested to make sure that it is not incorporated into T3/T4.
How do corticosteroids inhibit inflammation?
1) Inhibition of phospholipase A2 –> no arachidonic acid (LT/PG)
2) Inhibition of IL-2
3) Prevents release of histamine
What are the causes of Cushing’s syndrome?
Exogenous corticosteroids!!
Cushing’s disease (pituitary adenoma)
Ectopic ACTH (small cell lung carcinoma
Adrenal adenoma/carcinoma/nodular hyperplasia
Can distinguish somewhat using ACTH levels.
What is seen in Cushing’s syndrome?
Hypertension Moon facies, thin limbs, truncal obesity, buffalo hump Hyperglycemia Purple abdominal striae Osteoporosis Immune suppression Amenorrhea
What is seen with a normal Dex test?
Cushing’s disease?
Ectopic ACTH production?
Normal - cortisol levels inhibited by low dose
Pituitary adenoma - cortisol levels inhibited by high dose only
Ectopic - cortisol levels not affected by high dose
What is the treatment for Hyperaldosteronism?
Primary (Conn syndrome) - Surgical resection or Spironolactone
Secondary (CHF, etc.) - Spironolactone
What can cause secondary hyperaldosteronism?
CHF Renal artery stenosis Chronic renal failure Cirrhosis Nephrotic syndrome Reninoma
What hormones are affected in primary renal insufficiency?
Secondary?
Primary = all cortical hormones (Aldosterone, Cortisol, Sex)
Secondary = Cortisol & sex hormones (aldosterone controlled more by RAA axis)
How can primary and secondary adrenal insufficiency be distinguished?
Primary - Skin pigmentation & hyperkalemia
Secondary - no compensatory ^ in ACTH & no hypoaldosteronism
What can cause Addison’s disease?
Addison’s = chronic primary adrenal insufficiency
Autoimmune destruction TB dissemination Metastatic cancer (LUNG CANCER)
What are the adrenal medullae derived from?
Chromaffin cells of neural crest
What is seen with pheochromocytoma?
^serum Metanephrine & urinary VMA
Episodic: Headache ^Blood pressure Sweating Palpitations Pallor
What are the breakdown products of Dopamine?
NE?
EPI?
Dopamine –> HVA
NE –> Normetanephrine, VMA
EPI –> Metanephrine, VMA
What is the treatment for pheochromocytoma?
1) Alpha blockade (Phenoxybenzamine)
2) Beta blockade
3) Surgery
Alpha blockade must be given first to prevent hypertensive crisis (just like cocaine).
What is the most common adrenal tumor in children?
What is seen?
Neuroblastoma
Can be located anywhere along sympathetic chain
Small blue cell tumor
^HVA (dopamine metabolite) in urine
N-myc mutation
What is the 10% tumor?
Pheochromocytoma
10% malignant 10% bilateral 10% familial 10% extra-adrenal 10% calcify
What is seen in Hashimoto’s thyroiditis?
Transient hyperthyroid –> hypothyroid
Enlarged nontender thyroid
Anti-thyroglobulin Ab’s, Anti-TPO Ab’s (do not mediate dz)
What causes Hashimoto’s Thyroiditis?
What is seen on histology?
Autoimmune destruction of thyroid (HLA-DR5)
Hurthle cells
Germinal centers –> ^ risk of lymphoma
What is seen with cretinism?
“TAUS are retards”
Tongue enlargement Abdominal distension Umbilical hernia Skeletal abnormalities (short stature, craniofacial abn) Retardation
also jaundice, myxedema, hypotonia
What causes cretinism?
Severe fetal hypothyroidism
Maternal iodine deficiency (developing countries)
Defective T4 formation
Thyroid developmental failure
What is seen with subacute DeQuervain’s granulomatous thyroiditis?
Transient hyperthyroidism –> self-limited hypothyroidism
Follows a viral infection
TENDER THYROID
Granulomatous inflammation
What is seen with Riedel’s thyroiditis?
Hypothyroidism
Thyroid is replaced by fibrous tissue
Hard, rock/wood-like, painless goiter
Can involve local structures
Classically seen in younger patients (vs. anaplastic carcinoma which is older patients & can also involve surrounding structures)
What is the Jod-Basedow phenomenon?
Thyrotoxicosis seen when an iodine-deficient patient is given iodine. Seen in patients with multinodular goiter.
What is seen in Graves’ disease?
Histologically?
Hyperthyroidism
Exophthalmos & Pretibial myxedema (glycosaminoglycans)
Diffuse goiter
Histo: Large follicles with scalloped borders
What is seen in thyroid storm?
Underlying thyrotoxicosis + Stress (infection, surgery, etc.) –> T3/T4 & catecholamine surge –> Arrhythmia –> death
^Alkaline phosphatase may be seen
What are the types of thyroid cancer?
Papillary carcinoma (80%)
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoms
What is seen on with papillary carcinoma of the thyroid on histology?
Orphan Annie eyed nuclei
PSaMMoma bodies
Nuclear grooves
^risk with childhood irradiation
What is seen on with medullary carcinoma of the thyroid on histology?
Sheets of cells in an amyloid stroma
Amyloid is calcitonin
Associated with MEN2A & MEN2B
What causes primary hyperparathyroidism?
What is seen?
Parathyroid adenoma is most common cause
Hypercalcemia & “Stones, Bones, Groans, Psychic Moans”
Renal stones
Osteitis fibrosa cystica (cystic bone spaces, brown fibrous tissue)
Constipation
Depression, confusion
What is seen in the serum/urine with primary hyperparathyroidism?
Hypercalcemia Hypophasphatemia ^PTH ^Alkaline phosphatase ^cAMP in urine
What causes secondary hyperparathyroidism?
Chronic renal failure (high phosphate)
Most other causes of secondary hyperparathyroidism show low phosphate (^spilling at the PCT)
What is seen in Addison’s disease?
Addison’s = chronic primary adrenal insufficiency
Hypotension
Hyperkalemia
Metabolic acidosis
Skin hyperpigmentation (secondary ^^POMC–>ACTH/MSH)
What ketoacids are seen in DKA?
beta-hydroxybutyrate > acetoacetate
What is seen on labs in DKA?
Hyperglycemia
Anion gap metabolic acidosis
Ketones
Leukocytosis
Hyperkalemia (shifted from inside cells, actually low total body K+)
Hyponatremia (dilutional - serum osmolarity pulls H2O out of cells)
What is seen with carcinoid syndrome?
What is the treatment?
Most common tumor of the appendix, small bowel most common Diarhhea Flushing Asthmatic wheezing Right-sided valvular disease ^5-HIAA in urine Niacin deficiency
Tx: Octreotide (the tumors contain somatostatin receptors –> decreases 5-HT release)
What is seen in Zollinger-Ellison syndrome?
Gastrin-secreting tumor Found in pancreas or duodenum Recurrent ulcers Ulcers in jejunum Associated w/ MEN1
What is seen with MEN1?
Commonly presents with kidney stones & GI ulcers
Pituitary
Parathyroid
Pancreas (ZES, Insulinoma, VIPoma, Glucagonoma)
What is seen in MEN2A?
Parathyroid HYPERPLASIA
Medullary thyroid carcinoma
Pheochromocytoma
What is seen in MEN2B?
Marfanoid habitus
Oral ganglioneuromas
Medullary thyroid carcinoma
Pheochromocytoma
What mutation is seen in MEN?
MEN2A & MEN2B = ret mutation
What are the short acting insulins?
Long acting?
Short = Lispro & Aspart
Long = Glargine & Detmir
What is the mechanism of Metformin?
Decreases hepatic gluconeogenesis (primary)
Increases glycolysis
Increases peripheral insulin sensitivity
What is the mechanism of Sulfonylureas?
What are their toxicities?
Close K+ channel on beta cells –> ^insulin release
Requires some islet function so T2DM only
Toxicities:
Tolbutamide/Chlorpopamide - Disulfiram reaction
Glipizide/Glyburide/Glimepiride - Hypoglycemia
What is the mechanism of Thiazolidinediones?
What are their toxicities?
Pioglitazone & Rosiglitazone
Bind PPAR-gamma nuclear transcription factor –> ^insulin sens.
Toxicities: Weight gain Edema Hepatotoxicity Heart failure
“Ross is all Glitzed up for the PPARty, hope no one breaks his Heart”
What are the alpha-glucosidase inhibitors?
Acarbose & Miglitol
They inhibit intestinal brush-border glucosidases to delay glucose absorption –> decreased postprandial hyperglycemia
Can cause GI upset
What is the mechanism of Pramlintide?
Amylin analog –> decreased glucagon
Used to treat T1DM & T2DM
What are Exenatide & Liraglutide?
What toxicities are seen?
They are GLP-1 analogs used to treat T2DM. They cause ^insulin release and decreased glucagon release.
Toxicities:
N/V
Pancreatitis
What are the -gliptin drugs used for?
What are their toxicities?
Linagliptin, Saxagliptin, Sitagliptin
They are DPP-4 inhibitors used for T2DM
Toxicities:
Urinary or respiratory infections
What drugs are used for hyperthyroidism?
What are their side effects?
Methimazole, Propylthiouracil (PTU)
They are thyroid peroxidase inhibitors. PTU also blocks 5’-deiodinase to prevent T4–>T3 in peripheral tissues.
Toxicities: Agranulocytosis Aplastic anemia Hepatotoxicity (PTU) Methimazole is a teratogen
What conditions does octreotide treat?
Acromegaly Carcinoid syndrome Gastrinoma Glucagonoma Esophageal varices
What is exogenous oxytocin used for?
Induction of labor
Uterine contractions
Milk let-down
Control of uterine hemorrhage
What is Demecycline used for?
What toxicities are seen?
ADH-antagonist used for SIADH
(-vaptan drugs are also ADH antagonists)
Toxicities:
Nephrogenic diabetes insipidus
Photosensitivity
Bone/Tooth abnormalities
What clinical signs can test for hypercalcemia?
Chvostek’s sign - tapping facial nerve causes twitch
Trousseau’s sign - Inflation of BP cuff causes carpal spasm
What is seen with Lymphocytis hypophysitis?
Occurs during late pregnancy/early postpartum
Autoimmune destruction of pituitary
Acute headache
Bitemporal hemianopsia
Adrenal insufficiency
What is seen with a prolactinoma?
What is the treatment?
Most common type of pituitary adenoma
Bitemporal hemianopsia
Women - amenorrhea, galactorrhea
Men - low libido, infertility
Tx: Bromocryptine (dopamine agonist)
How is acromegaly diagnosed?
What is the treatment?
^serum IGF-1
serum GH not suppressed following oral glucose tolerance test
Pituitary mass on MRI
Tx: Surgical excision and/or Octreotide (somatostatin)
What can cause diabetes insipidus?
Central - pituitary tumor, trauma, surgery, histiocytosis x
Nephrogenic - hereditary, hypercalcemia, lithium
What lab findings are seen with diabetes insipidus?
What tests are done?
Urine specific gravity < 1.006
Serum osmolarity > 290 mOsm/L
Water deprivation test:
Urine osmolarity doesn’t ^
Response to desmopressin differentiates central/nephrogenic
What is the treatment for diabetes insipidus?
Central - Intranasal desmopressin (ADH)
Nephrogenic - Hydrochlorothiazide
What can cause SIADH?
Ectopic ADH secretion (small cell lung carcinoma)
CNS tumors/head trauma
COPD
Cyclophosphamide
What is seen in SIADH?
^ADH secretion –> secondary hypoaldosteronism –> hyponatremia w/ near-normal volume status
Seizures can be seen with severe hyponatremia
What is the treatment for SIADH?
Fluid restriction IV saline (to correct hyponatremia) -vaptan drugs (ADH antagonists)
What can cause hypopituitarism?
Nonsecreting pituitary adenoma/Craniopharyngeoma
Sheehan’s syndrome:
intrapartum blood loss –> failure to lactate & loss of pubic hair
Empty sella syndrome:
atrophy or compression, seen in obese women
Brain injury/hemorrhage
Radiation
What is seen with an insulinoma?
Episodic hypoglycemia w/ mental status changes
Low glucose
High insulin
High C-peptide (vs. exogenous insulin administration)
What is seen with a somatostatinoma?
Achlorhydria (inhibition of gastrin)
Cholelithiasis & steatorrhea (inhibition of CCK –> no GB contraction)
What aspects of diabetes cause the chronic effects seen?
Nonezymatic glycosylation (large & small vessel disease)
Osmotic damage (Schwann cells, cataracts) Preferentially occurs in cells with aldose reductase & insufficient aldose dehydrogenase
What is seen on pancreatic histology in T1DM?
T2DM?
T1DM - WBC infiltrate (Type IV hypersensitivity)
T2DM - Amyloid deposition (Amylin = Islet Amyloid Polypeptide)
What type of diabetes is strongly correlated to genetics?
T2DM is more genetically influenced
Both T1DM & T2DM are polygenic
