Endocrine Flashcards
Embryological origin of thyroid, parathyroid and pancreas
Endoderm
Embryological origin of hypothalamus, anterior pituitary, posterior pituitary, adrenal medulla, and C cells of thyroid
Ectoderm
Embryological origin of adrenal cortex and gonads
Mesoderm
Zona glomerulosa responds to and secretes
Renin-angiotensin; Aldosterone
Zona Fasciculata responds to and secretes
ACTH, CRH; Cortisol
Zona Reticularis responds to and secretes
ACTH, CRH; sex hormones (androgens)
Chromaffin cells of adrenal medulla respond to and secrete
Preganglionic sympathetic fibers; Catecholamines (Epinephrine)
Which four hormones share a common alpha subunit?
TSH, FSH, LH, hCG
Which anterior pituitary hormones are basophiles?
FSH, LH, ACTH, TSH
Which part of the hypothalamus produces vasopressin (AVP/ADH)?
Supraoptic nucleus
Paraventricular nucleus of hypothalamus forms which hormone
Oxytocin
Which Glucose transporter is Insulin-dependent
GLUT-4
Where are GLUT-4 transporters located
Adipose tissue and striated muscle tissue
Name the Insulin-independent GLUT transporters
GLUT-1, 2, 3, 5
Where is GLUT-1 found
Brain, RBCs, cornea, placenta
Where is GLUT-2 found and why is it special
pancreatic beta cells, liver, kidney, small intestine; bidirectional glucose transport
Where is GLUT-3 found
brain, placenta
Where is GLUT-5 (Fructose) found
spermatocytes, GI tract
What are the insulin-independent glucose organs
Brian, RBCs, Intestine, Cornea, Kidney and Liver
does insulin cross the placenta
No
Does glucagon cross placenta
yes
Why do you have greater insulin release with oral intake of glucose?
Incretins like GLP-1 are released after meals ad increase beta cell sensitivity to glucose via GLUT-2
Which hormone increases release of ACTH, MSH and beta-endorphins
CRH released by hypothalamus
Which hormone is inhibited by chronic steroid use
CRH
Which hormone decreases prolactin and TSH
Dopamine
How do dopamine antagonists (anti-psychotics) cause galactorrhea?
They decrease inhibition of prolactin
Where in the hypothalamus is CRH synthesized
paraventricular nucleus
Where in hypothalamus are dopamine and GHRH synthesized
Arcuate nucleus
Function of GHRH
Stimulate release of GH from Anterior pituitary
The analog (tesamorelin) of which hormone is used to treat HIV-associated lipodystrophy?
GHRH
From where is GnRH released?
medial-preoptic nucleus
What is the difference between tonic and pulsatile release of GnRH
Tonic release suppresses HPG axis while pulsatile leads to puberty and fertility by increasing FSH and LH release
Which hormone inhibits GnRH
Prolactin
Signs of pituitary prolactinoma
amenorrhea, osteoporosis, hypogonadism and galactorrhea
Which hormone decreases release of GH and TSH
Somatostatin
Which hormone increases release of TSH and prolactin
TRH
Which hormone is prolactin structurally similar to
Growth hormone
Stimulates milk production, inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH
Prolactin
Excess is associated with decreased libido
Prolactin
How can primary or secondary hypothyroidism cause prolactinemia?
TRH stimulates prolactin secretion
GH + IGF-1 lead to which changes
increaesd linear and muscle growth, increased insulin resistance
When is growth hormone secretion increased
Exercise, deep sleep, puberty, hypoglycemia
Where is Ghrelin-produced
stomach
Which two conditions increase Ghrelin production
sleep deprivation and Prader-Willi syndrome
Which tissue produces leptin
Adipose tissue
Where do endocannabinoids act
Hypothalamus or nucleus accumbens (food intake)
How can exogenous corticosteroids cause reactivation of TB and candidiasis
Decrease IL-2 secretion and suppress immune response
How does cortisol suppress the immune response
Inhibits LTE and PGE release, inhibits WBC adhesion, inhibits Histamine release from mast cells, decreases eosinophils, inhibits IL-2 production
How does alkalosis cause hypocalcemia
Increases affinity of serum Ca+2 for albumin
Symptoms of hypocalcemia
cramps pain, parasthesia, carpopedal spasms, Chvostek and Trosseau sign
What is the function of Active Vitamin D (1,25-OH2)
Increase absorption of Ca+2 and PO4 in gut
What is the source of PTH?
Chief cells of parathyroid
Four common causes of Magnesium loss
Aminoglycasides, diarrhea, alcohol abuse and diuretics
Four functions of PTH
Increse bone resorption of Ca+2 and PO4
Increase kidney reabsorption of Ca+2 in DCT
decrease reabsorption of PO4 in PCT
increase calcitriol production by stimulating kidney 1 alpha-hydroxylase in PCT
Which three factors increase PTH secretion?
decrease Ca+2, decrease Mg+2(initially, substantial decrease inhibits it), increase PO4
What is the source of calcitonin
Parafollicular (C) cells of thyroid
What is the function of calcitonin
oppose actions of PTH by decreasing bone resorption of Ca+2
What is the major function of thyroid hormone
Regulate body’s metabolic rate
Which factors increase and decrease TBG respectively
increase: pregnancy and OCP (estrogen)
decrease: hepatic failure, steroids
What is the Wolff-Chaikoff effect
excess iodine temporarily inhibits TPO leading to decreased T3/T4
Which hormones use the cAMP signaling pathway (FLAT ChAMP)
FSH, LH, ACTH, TSH, CRH, hCG, ADH, MSH, PTH, calcitonin, GHRH, glucagon
Which hormones use the cGMP pathway BAD GraMPa
BNP, ANP, EDRF (NO)
Which hormones use the IP3 pathway? (GOAT HAG)
GnRH, Oxytosin, ADH (V1R), TRH, Histamine, Angiotensin II, Gastrin
Which hormones use Receptor Tyrosine Kinase? (MAP kinase pathway)
Insulin, IGF-1, FGF, PDGF, EGF (growth factors)
Which hormones use Nonreceptor Tyrosine Kinase (PIGGlET- acidophiles and cytokines) – JAK/STAT pathway
Prolactin, immunomodulators (cytokines IL-2, IL-6, IFN), GH, G-CSF, EPO, TPO
What does increased sex hormone binding globulin cause in men?
Gynecomastia
What does decreased sex hormone binding globlulin cause in women?
Hirsuitism
Symptoms of Sheehan syndrome
Fatigue, loss of pubic hair, and poor lactation after giving birth (preceded by blood loss)
Etiology of Sheehan Syndrome
Pituitary grows in pregnancy, blood supply cannot meet demand and leads to pituitary infarct
Which drugs can cause nephrogenic diabetes insipidus?
Lithium and demeclocycline
Most common cause of SIADH
Small cell carcinoma in the lung
What condition does demecocyline treat?
SIADH
Clinical features of SIADH
Hypertension, Isovolemic hyponatremia and low serum osmolality
Mental status changes and seizure s
Which part of the neck does thyroglossal duct cyst present
Anterior neck mass
Thyrogloossal duct cyst is a failure of
Involution
Where does lingual thyroid present
Base of tongue
Four Bs of thyroid function
Basal metabolic rate
Brain growth
Bone growth
beta-adrenergic receptor expression increase
What causes increased BMR in hyperthyroidism?
Excess thyroid hormone causes production of more Na+/K+ ATPase
Lid lag is specific for which thyroid condition
Graves disease
What is thyrotoxic myopathy
Proximal muscle weakness with normal CK, seen in hyperthyroidism
Four causes of nodular goiter
Toxic multinodular goiter
Thyroid adenoma
Thyroid cancer
Thyroid cyst
Four causes of smooth/diffuse goiter
Graves disease
Hashimoto Thyroiditis
Iodine deficiency
TSH-secreting pituitary adenoma
What cause exophthalmos and pretibial myxedema in Graves disease
Fibroblasts behind orbit and shin express TSH receptor, which is overstimulated and produces GAGs, fibrosis and edema buildup
What causes hypcholesterolemia in hypothyroidism
Increase bile excretion and increased LDL gene receptor activity (even though HMG CoA Reductase activity increases)
Common clinical features of hyperthyroidism
Heat intolerance, weight loss, increase appetite, hyperactivity, anxiety, insomnia, hand tremor
brisk reflexes, diarrhea, myxedma, chest palpitations/arrhythmias, hypocholesterolemia
Lab findings of hyperthyroidism
Decreased TSH if primary (Graves), increased free or total T3, T4; hypocholesterolemia
What causes diffuse goiter appearance in Graves disease
Constant TSH stimulation by IgG leads to thyroid hyperplasia and hypertrophy
What type of hypersensitivity reaction is Graves disease
Type II
How does pregnancy affect thyroid levels
Increases TBG so increases total thyroid levels since more T4 binds to it, but does not increase free T3 or T4
How does Graves cause hyperglycemia
Stimulates gluconeogenesis and glycolysis
What causes a thyroid storm and what is its treatment
Elevated catecholamines in hyperthyroid patient during stress (surgery, childbirth); tx is PTU
Symptoms of thyroid storm
Arrhythmia, hyperthermia, vomiting and hypovolemic shock
Which test is best for screening thyroid dysfunction?
TSH
Usual cause for nodular goiter
Iodine deficiency
What is the function of Iodine-123 uptake test?
Evaluate acitivity of thyroid gland
Increased uptake = hot nodule (increased TH synthesis)
Decreased uptake = cold nodule
Mental retardation, enlarged tongue, short stature, skeletal abnormalities and short stature in a child are indiicative of
Cretinism
What causes cretinism in neonates and infants
Hypothyroidism of mother in early pregnancy; need thyroid hormone for normal brain devo and skeletal devo
Clinical feature of myxedema in hypothyroidism
Deep voice, large tongue (GAG accumulation in soft tissue and skin)
General symptoms of hypothyroidism
cold intolerance, weight gain, constipation, facial/periorbital myxedema, dry skin and brittle hair, bradycardia
What is hypothyroid myopathy
proximal muscle weakness with increased CK
Lab findings in hypothyroidism
increased TSH (if primary.. Hashimoto); decreased free T3, T4, hypercholesterolemia
Presentation of myxedema coma
Progressive stupor, hypothermia, bradycardia, hypoglycemia, hypocortisolism, SIADH
Findings of pheochromocytoma
increased catecholamines and metanephrines in urine and plasma
Treatment for Pheochromocytoma
Phenoxybenzamine (irreversible alpha antagonist) followed by beta-blocker
What type of hypersensitivity reaction is Hashimoto thyroiditis
Type 2 or Type 4
3 clinical features of Hashimoto Thyroiditis
Initial presentation of hyperthyroidism due to follicle damage
Progresses to hypothyroidism; decreased T4, increased TSH
Anti-thyroglobulin and antiTPO antibodies
Hurthle cells are inidicative of which condition
Hashimoto thyroiditis
Hashimoto thyroiditis increases risk of which lymphoma
B cell marginal zone lymphoma (presents as enlarging thyroid gland in late disease)
Characteristic feature of De Quearvain (Acute) Thyroiditis
Tender thyroid with symptoms of hyperthyroidism following a viral infection; self-resolving
Histology of Hashimoto
Lymphocytic germinal centers/infiltration with Hurthle cells (eosinophilic large cells)
Histology of De Quervain thyroiditis
Granulomatous inflammation with multinucleated giant cells, decreased I-123 uptake
“Hard as wood” nontender thyroid gland is indicative of
Riedel fibrosiing thyroiditis
What is the risk of Riedel fibrosing thyroiditis
Fibrosis may extend to airway and lead to shortness of breath; treat wit corticosteroids or tamoxifen
What causes Hashimoto thyroiditis?
Autoimmune destruction of thyroid gland; associated with HLA-DR5
Most commmon cause of Cretinism in US
Thyroid dysgenesis
6 Ps of cretinism
Pot-bellied, Pale, Puffy face, Protruding uumbilicus, Protruding tongue, Poor brain development
4Ps to treat Thyroid Storm
Propanolol, PTU, Prednisolone, Potassium iodide
What is Jod-Besedown phenomenon
Giving iodine to pt who has iodine deficiency but hot thyroid nodule causes thyrotoxicosis
Why do cold nodules warrant biopsy
They are usually seen in adenoma or carcinoma
What is Orphan Annie Eye cell and what is it indicative of?
Cell with white clearing center of nucleus and nuclear groove; indicates Papillary carcinoma
What are Psammoma bodies indicative of
Papillary carcinoma
How does follicular thyroid carcinoma spread
Hematogenously
Medullary carcinoma of thyroid is associated with which gene mutation?
RET (MEN2A, MEN2B)
What is the MEN2A triad
Medullary carcinoma, pheochromocytoma, parathyroid adenoma
What is the MEN2B triad
Medullary carcinoma, pheochromocytoma, ganglioneuroma of oral mucosa
Medullary carcinoma is malignant spread of which cells
Parafollicular C cells (Secrete calcitonin, lowers serum calcium)
Histology of medullary carcinoma of thyroid
Calcitonin cell deposits in amyloid stroma (a bunch of purple cells surrounded by pink)
Anaplastic carcinoma is a poor prognosis malignant thyroid cancer seen in which population
Elderly (prsents as dysphagia or respiratory compromise)
Lab findings for primary hyperparathyroidism
Increased: PTH, calcium, urine CAMP, alkaline phosphatase
Decreased: phosphate
Potential complications of hyperparathyroidism due to hypercalcemia
Nephrolithiasis (calcium oxalate), nephrocalcinosis (renal insufficiency and polyuria)
CNS disturbances, constipation, acute pancreatitis, steitis fibrosa cystica
How can hyperparathyroidism lead to acute pancreatitis
Ca+2 activates pancreatic enzymes (zymogens) within pancreas, causing damage
Autosomal dominant Pseudohypoparathyroidism presents as
Hypocalcemia, increased PTH, mutation in Gs, short stature, short 4th and 5th digits
Short 4th and 5th digits with hypocalcemia likely indicate
Pseudohypoparathyroidism
“Stones, bones, groans and psychatric overtones” applies to
Primary hyperparathyroidism
Osteoclasts and deposited hemosiderin from hemorrhages “brown tumor” is indicative of
Osteitis fibrosa cystica from hyperparathyroidism
What causes type 1 diabetes mellitus
Autoimmune destruction of beta cells (antibodies against glutamic acid decarboxyalse)
What type of hypersensitivy reaction is T1DM
Type IV
Best diet advice for T2DM
Control fat intake and weight control
Clinical findings of MEN1
Pituitary adenoma, hyperparathyroidism, pancreatic tumors
Tumor of islet cells is associated with which condition
MEN1
Watery diarrhea, hypokalemia and achlorydia suggest which pancreatic neoplasm
VIPoma
Treatment-resistant ulcers extending into jejunum suggest which pancreatic neoplasm
gastrinoma
Achlorydia and cholelithiasis with steatorrhea are suggestive of which pancreatic neoplasm?
Somatostatinoma
Hypertension, hypokalemia and metabolic alkalosis suggest which condition
Hyperaldosteronism
Aldosterone function
Increase sodium reabsorption in PCT, increase K+ secretion in DCT/CCT
Most common cause of primary hyperaldosteronism
Bilateral adrenal hyperplasia, and adrenal adenoma (Connn syndrome)
Difference between primary and secondary hyperaldosteronism
Primary has low renin and high aldosterone, secondary has high renin and high aldosterone
AD excess expression of aldosterone synthase in fasciculata
Familial hyperadosteronism
Clinical presentation of familial hyperaldosteronism
HTN, hypokalemia and high aldosterone with low renin in children. Responds to dexamethasone
Why do you get diffuse skin pigmentation in 21-hydroxylase deficiency?
Body isn’t producing cortisol or aldosterone, so increased ACTH activity
Males with ambiguous genitalia at birth and hypokalemic hypertension suggest which CAH
17-alpha-hydroxylase deficiency
A girl who has no secondary sexual development and presents with hypokalemic hypertension most likely has
17-alpha-hyrdoxylase deficiency
Which CAH is most common
21-hydroxylase deficiency
Decreased mineralocorticoids and decreased glucocorticoids with increased sex hormones indicates which CAH
21 hydroxylase deficiency
Ambiguous female genitalia and precocious puberty in both sexes implies which two CAHs
11-beta-hydroxylase deficiency or 21-hydroxylase deficiency
Why is edema absent in hyperaldosteronism induced hypertension?
Aldosterone escape mechanism causes natriuresis
First-line treatment for hyperaldosteronism
Spironolactone or eplerenone
What is Liddle syndrome
AD, decreased degradation of Na channels in collecting duct, leading to hyperaldosteronism-like symptoms (hypokalemia, hypernatremia, hypertension, metabolic alkalosis in young patient)
Lab values of aldosterone and renin in Liddle syndrome
low aldosterone and low renin
Treatment for Liddle syndrome
Potassium-sparing diuretics (triamterene and amiloride), block Na+ channels in CCT
Which gene mutations increase risk of papillary carcinoma?
RET and BRAF
How is pseudohypoparathyroidism inherited?
Through mother by imprinting
How is pseudopseudohypoparathyroidism inherited and how is it different from pseudohypoparathyroidism?
Inherited from father due to imprinting. No end-organ PTH resistance
How does hypercortisolism lead to hypertension and hypokalemia
Cortisol increases peripheral vascular sensitivity to catecholamines (constriction) and at high levels can cross react with aldosterone receptors
Muscle weakness with thin extremities, moon facies, buffalo hump, purple striae, truncal obesity, hypertension with metabolic alkalosis, oosteoporsis and immune suppression indicate
Hypercortisolism
How does hypercortisolism (Cushing syndrome) lead to immune suppression?
Inhibits phospholipase A2, IL-2 and Histamine
Diagnosis of Cushing syndrome
1) 24-hour urine cortisol (increased)
2) late-night salivary cortisol level (increased)
3) Low-dose dexamethosone suppression test
What is the purpose of plasma ACTH test
Distinguishes ACTH-dependent causes of Cushing syndrome from ACTH-independent
Difference between low-dose and high-dose dexamethosone test
Low-dose suppresses cortisol in normal individuals
High-dose suppresses ACTH production by pituitary adenoma but not by ectopic source
Difference between Cushing syndrome and Cushing disease
Cushing syndrome is hypercortisolism in general, Cushing disease is hypercortisolism caused by pituitary adenoma
Why does hypercortisolism cause weak, thin extremities
Breaks down muscle to release amino acids for gluconeogenesis
Why does hypercortisolism cause buffalo hump, moon facies, and truncal obesity?
Increases insulin resistance, and storage of fat centrally
Why does hypercortisolism cause purple striae?
Impaired collagen synthesis leads to thinning of skin
Hypotension, hyperpigmentation, vomiting, diarrhea and hyperkalemia and hyponatremia suggest which adrenal insufficiency disorder?
Addison disease (destruction of adrenal glands)
Most common cause of Addison disease in developing world
TB
Which three hormones does POMC produce?
beta-endorphins, ACTH, MSH (melanin)
3 gene mutations associated with pheochromocytoma
MEN2, VHL, NF1
What is the mechanism of phenoxybenzamine?
irreversible alpha blocker
Why is phenoxybenzamine used before adrenal medulla excision
catecholamines can leak out during excision surgery and cause hypertensive crisis so phenoxybezamine prevents this
Inheritance of MEN syndromes
Autosomal dominant
Pheochromocytoma, Medullary thyroid carcinoma, Mucosal neuromas
MEN2B
Which MEN is associated with marfanoid habitus
MEN2B
Parathyroid hyperplasia, pheochromocytoma, Medullary thyroid carcinoma
MEN2A
Pituitary tumors, Pancreatic endocrine tumors (ZE syndrome, insulinomas, VIPomas), Parathyroid adenomas
MEN1
Diagnosis of acromegaly
Increased serum IG-1, failure to suppress GH with oral glucose tolerance test, pituitary mass on MRI
Laron syndrome features
Saddle nose, prominent forehead, small head circumference, short height, small genitalia, delayed skeletal maturation
increase GH but decreased IGF-1
What is the most common cause of death in children with Gigantism?
heart failure
A patient comes in complaining of a painful rash involving her groin and legs that has been worsening over time. Her PMH includes diabetes mellitus and occasional loose stools (GI sx). The rashes are erythematous plaques with crusting and scaling at borders. They are necrolytic and migratory. This suggests which condition?
Glucagonoma (pt will have hyperglycemia)
