Endo Flashcards
What is the foramen cecum?
- Divot on tongue from obliteration of thyroglossal duct
- Where the thirds of tongue meet
What are parafollicular cells?
- Cells in between thyroid follicles that secrete calcitonin
- Derived from neural crest cells
Where is calcitonin produced?
Parafollicular cells of the thyroid
What type of cancer does neoplasia of parafollicular cells produce?
Medullary thyroid cancer - progress can be tracked by measuring calcitonin levels
Where are branchial cleft cysts found? Thyroglossal duct?
Branchial: sides of neck
Thyroid: midline, will move with tongue movement as are attached to foramen cecum
Venous drainage of adrenals?
Left: renal vein, IVC
Right: IVC
Layers of adrenal cortex and what is produced?
Glomerulosa: Mineralocorticoids - aldosterone
Fasciculata: Corticosteroids - cortisol
Reticularis: Androgens
Regulation of adrenal cortex?
ACTH (Adrenocorticotropic hormone): regulates reticularis / fasciculata
Renin: Glomerulosa
What are the adrenal medulla and cortex derived from?
Cortex: Mesoderm
Medulla: ectoderm -> neural crest
What does the adrenal medulla secrete? How is it regulated?
- Epi and NE into the bloodstream when
- Preganglionic SNS neuron release ACH (acetylcholine) directly onto Nicotinic receptors of the medulla
Where is the pituitary gland found?
In the sella tursica
What is the anterior pituitary derived from?
Rathke’s pouch / surface ectoderm
Another name for anterior / posterior pituitary?
Anterior: adenohypophysis
Posterior: neurohypophysis
What is posterior pit derived from?
Neuroectoderm, just like the adrenal medulla
What do the nueral crest and neuroectoderm become?
Crest: PNS
Derm: CNS
How does hypothalamus communicate with anterior?
Trophic hormones released into portal capillary system causing release of new hormones from anterior
How does hypothalamus communicate with posterior?
- No portal system, axonal projections form hypo to post
- Hormones made in hypo and moved down axons by neurophysins
What do basophils and acidophils of anterior secrete?
Acidophils: secrete prolactin and GH
Basophils: everything else
Which pituitary hormones share same alpha subunit?
- FSH
- LH
- TSH
* ***B-HCG shares this sub unit two so can act as TSH in high enough doses
Hormones from posterior pit?
Vasopressin: Supraoptic nuclei
Oxytocin: Paraventricular neclei
What are the islets of langerhan?
Bodies of alpha and beta cells in pancreas:
Beta cells: insulin
Alpha cells: glucagon
Delta: somatostatin
3 places glucose can be stored?
- Skeletal muscle
- Liver
- Adipose tissue
Does insulin control glucose transport at liver?
No, but does increase glucose metabolism
Does liver prefer to metabolize glucose into glycogen or fatty acids?
Glycogen, has small capacity though, so quickly begins making triglycerides to send off in VLDLs
Insulin impact on fat and muscle metabolism?
- Decreased lipolysis
2. Increased AA uptake and protein construction
How is glucose formed?
- Found in vesicles in B cells as proinsulin
- Cleaved in vesicle forming C peptide and active insulin
How to tell between high endogenous/exogenous insulin?
Endogenous will have CRP high as well
Mechanism of insulin release?
- Glucose enters Beta via GLUT2
- Converted to ATP
- ATP deactivates K leak channel increasing [K]
- Beta cell depolarizes from + charge
- Ca now enters cell = insulin release
What is GLP-1?
- When GI cells sense sugar, release GLP-1 leading to insulin release before sugar hits bloodstream
- This is why oral glucose spikes insulin higher than IV
How does insulin signal at cell?
- Binds membrane tyrosine kinase autophosphorylation
- MAPK goes to nucleus
- PI3K works on cytoplasm
Where is GLUT4 found?
- Muscle and adipose tissue
- Insulin causes it to integrate in cell membrane
Why does exercise help diabetes?
Exercise induces GLUT4 insertion in skeletal muscle just as insulin does
* Can lead to HYPOglycemia if dont drop insulin levels before exercising
How is glucose transported in liver?
- GLUT2 transporter - not dependant on insulin
How does GLUT2 work?
- Found in Liver and Beta cells
- By directional allowing liver to release glucose in fasting state
- Maxes out transport later than GLUT4
GLUT4 vs. GLUT2 kinetics?
GLUT4: lower Km, ramps up faster
GLUT2: higher vMAX, can handle higher loads
Where are gluco/hexokinase found?
Gluco: liver
Hexo: everywhere else
Characteristics of GLUT1/3 and where are they found?
High affinity high capacity glucose transport:
- Brain
- RBC: no mitochondria so only energy comes from anaerobic glucose metabolism
- Placenta
- Cornea
What is GLUT5?
- Fructose transporter found in SI allowing fructose to be absorbed and turned into glucose for rest of body to use
- Also found in sperm
Glucagon signaling path?
G coupled increase cAMP, increased PkA
What is a trophic hormone?
Impact on target leads to release of another hormone: for example TSH leads to TH release from thyroid
What is somatostain
AKA: GHIH “Growth hormone inhibiting hormone”
- Remember that this is same hormone that brings GI activity to a halt
How is prolactin regulated?
Dopamine inhibits prolactin
What does prolactin regulate?
- Inhibits GNRH shutting down production of sex hormones
Which drugs will lead to increased prolactin?
Antipsychotics: if they are inhibiting DE prolactin is no longer being inhibited
Impact of TH/TRH on prolactin?
Both increase prolactin
- Elevated TRH would be see in HYPOthyroid
Somatostatin impact on TH?
Decreases it
What does prolactin do?
- Stimulates breasts to produce milk
- DOES NOT cause milk to be released
- Let down is they job of oxytocin
Why isn’t there milk DURING pregnancy?
- Progesterone is inhibiting prolactin
- Once placenta is delivered, progesterone drops allowing for Milk to be made
What is another name for GH?
Somatotropin
Functions of GH?
- Bone lengthening: kids
- Bone strengthening: adults
- Protein synthesis
- Lipolysis / gluconeogenesis `
What are some natural factors that stimulate GH?
- Sleep
- Exercise
- Arginine (glucose decreases)
- Puberty
2 hormones causing insulin resistance?
- GH
2. Cortisol
What regulates most effects of GH?
IFG-1
What is ghrelin?
“Hunger hormone”
- Secreted by stomach when empty
- Acts on lateral hypothalamus
- **Activity in laterally nuclei makes you hungry = grow laterally
What is leptin?
- Secreted by fat cells when full of fat
- Acts on medial thalamic nuclei
What does sleep do to hunger hormones?
- Increases ghrelin = grow laterally
- Decrease leptin = implicated in congenital obesity
Thirst receptors in brain and what are they sensing?
- Arterial baroreceptors: HYPOvolemia
2. OSMOreceptors: HYPERtonicity
Is ADH or aldosterone regulating osmolality of blood?
ADH
***Since aldosterone brings in Na/H2O it is not changing the tonicity of the water
Actions of ADH and receptors?
V2: Free water retention
V1: arterial constriction
**Think Vasopressin as it is a pressor
What is the precursor to all steroids? Rate limiting step?
Cholesterol: conversion to pregnenolone is rate limiting
What controls entry to steroid synthesis pathway?
ACTH
What enzyme is not found in z. glomerulosa?
17-a-hydroxylase which is needed for cortisol
What is necessary to enter cortisol pathway?
17-a-hydroxylation of pregnenolone or progesterone
2 Enzymes necessary to make aldosterone and Cortisol?
- 21-hydroxylase
2. 11-B-hydroxylase
Do precursors to mineralocorticoids of mineral or glucocorticoid activity?
Mineral
Final regulation in aldosterone pathway?
Angiotensin II
What is happening in CAH?
“Congenital adrenal hyperplasia”
- Defect in an enzyme necessary for creation of cortisol
What feedback happens when cortisol is low?
- ACTH increases increasing amount of cholesterol heading into the adrenal cortex
- ACTH also causes hypertrophy of cells in all layers of cortex
Role of androgens?
- External male genitals in fetus
2. Male secondary characteristics in adolescence
Most common form of CAH? What happens?
21-a-hydroxylase deficiency
- Needed or production in both reticularis and fascicularis
- Sex steroid path is only one functioning
- Virilization in females
- Precocious puberty in males
- Decreased BP with HYPER K
What happens in 11-B-hydroxylase deficiency?
- Female virilization
- Normal or precocious males
- No cortisol
- Increased minerals as all precursors have mineral activity
- High BP with HYPO K
What happens in 17-a-hydroxylase deficiency?
- Increased minerals: High BP with HYPO K
- Decreased androgens: boys with ambiguous genitals, girls may not develop secondary sex characteristics at puberty
What does 5-a-reductase do?
DHT creation from androgens
What are flutamide and finasteride?
Finasteride: androgen receptor blocker
Flutamide: blocks 5-a-reductase
Effects of cortisol?
- Increased arterial A1: high BP
2. Stronger catabolic effects than glucagon
Extra effects cortisol has that glucagon does not?
- Proteolysis
- Insulin resistance
- Osteo/fibroblast inhibition leading to bone and connective tissue weakness
- Immunosuppression
- Anxiety, depression, psychosis
What are some things cortisol shuts down in immune?
- Phospholipase A: no AA release
- IL2: no T cell proliferation
- Neutrophils adhesion: false neutrophilia
- Decreased EOSs and blocks histamine
Breakout of Ca in blood?
- Free: 45%
- Bound to albumin: 45%
- 10%: bound to anions other than albumin
What does acidosis do to Ca?
- Causes HYPERcalcemia
- H+ is competing with Ca to bind to anions so this increases free Ca in blood
What is cholecalciferol?
Vitamin D - steroid hormone
What is hydroxyapatite?
Combination of Ca / PO4 that makes up majority of bone mineral
Vitamin D?
- Increased absorption of both Ca and PO4
- Decreased Ca excretion at kidney
- Increased osteoclast activity for remodeling
3 things stimulating 1-a-hydroxylation of vitamin D in kidney?
- Low Ca
- Low PO4
- PTH
PTH relation to osteoclasts?
- Osteoclasts have RANK receptor but not PTH
- PTH receptor on osteoblast leads to rank-L secretion
PTH impact on kidney?
- Increased Ca resorption
- Increased PO4 excretion
- Increased vitamin D activation
Regulation of PTH?
Increased by:
- Low Ca
- High Po4
- Low Mg
* ***Super low Mg inhibits PTH though
Function of calcitonin?
- Stops osteoclast resorption
- Stops gut Ca absorption
- Increased Ca renal excretion
* **CalcitonINNNNN wants to keep Ca innnnnn Bones, not in blood
Cancer known to secrete PTH and what will it cause?
Squamous cell lung cancer
- Decreased bone density
- Decreased serum phosphate
Effects of TH?
- Increased B receptor activity: Increased HR / contract
- Increased SNS activity - Increased energy and alertness
- Increased metabolism: increased Na/K ATPase synthesis
- Heat generation / weight loss - Bone Growth
- CNS maturation
- Endometrial development
What is increased appetite and weight loss indicative of?
HYPERthryroid
Difference between T3/4?
T4: secreted by thyroid but is weaker version
T3: Stronger version with an iodine cleaved by peripheral tissue
What happens to TH in liver failure?
- TH is highly lipophilic so needs to be bound by TBG in serum
- TBG decreases in liver failure increasing TH
- ***Free T4 will be high but total will be low because free is inhibiting TSH and TRH
What can decrease TBG?
- Nephrotic syndrome
- Liver failure
- Corticosteroids
What can increase TBG?
- Pregnancy
2. Exogenous estrogen
2 ingredients in TH?
- Iodine
2. Tyrosine
What is thyroglobulin?
TH precursor that will be combined with Iodine in lumen to make TH
What does thyroid peroxidase do?
- Oxidizes Iodide -> iodine
- Iodinates thyroglobulin
- Makes T3/4 from globulins
How does TH increase metabolism?
Increases action of Na/K ATPase
Where to lipophilic hormones bind?
Intracellular receptors
What are the lipophilic hormones?
- Vitamin D
- Sex hormones
- Adrenal hormones
- TH
How do all vasodilators work? What are they?
Activating guanylyl cyclase increasing cGMP
- NO
- ANP
- BNP
How do the FLAT hormones signal?
- Gs receptor increasing cAMP
1. FSH
2. LH
3. ACTH
4. TRH
How do the Pig hormones signal?
Receptor associated tyrosine kinases
- Prolactin
- GH
What molecules signal with tyrosine kinase?
Receptor associated: 1. PiG: prolactin and GH 2. Immunomodulators 3. EPO / thrombopoietin 4. GCSF Intrinsic tyrosine: 1. Insulin 2. IGF-1
What is Gs/q coupled with?
Gs: cAMP, decreased Ca, vasodilation
Gq: IP3, increased Ca, Constriction
Endocrine hormones signaling via cAMP?
"FLAT CHAMP" FSH LH, ACTH TSH
CRH /calcitonin hCG ADH: V2-receptor MSH PTH ***GHRH / glucagon
What signals via IP3?
"GOAT HAG" GnRH Oxytocin ADH: V1 TRH
Histamine: H1
Angiotensin II
Gastrin
Which are the receptor associated tyrosine kinase hormones / JAK / STAT?
"PIGG lET" Prolactin Immunomodulators GH G-CSF
Erythropoietin
Thrombopoietin
How does non functional pituitary adenoma present?
Mass effect:
- Bitemporal hemianopsia: adjacent to optic chiasm
- Headache
- HYPOpituitarism
What is adjacent to sell turcica?
Optic chiasm, this is why pituitary adenoma will cause bitemporal hemianopsia
What is bitemporal hemianopsia?
Inability to see objects in peripheral fields of vision
Presentation of prolactinoma in men and women?
Men: Headache and decreased libido
- No galactorrhea as men dont have lobules
Women: Galactorrhea and amenorrhea
- This is because prolactin suppresses GNRH
What is bromocriptine?
Dopamine agonist: can be used to treat prolactinoma as DE suppresses prolactin
Why does GH adenoma lead to gigantism in kids but acromegaly in adults?
Adults have already fused epiphyseal growth plates long bones can no longer grow
What often occurs secondary to GH adenoma and why?
- Secondary diabetes as GH decreases glucose uptake
How do diagnose GH adenoma?
- Increased GH
- Increased IGF-1
- Oral glucose does not suppress GH
Treatment of GH adenoma?
- Octreotide: somatostatin analog
* **Remember that another name for somatostatin is “Growth hormone inhibiting hormone” and that it is also the thing that slows everything down in the gut
What is octreotide?
Somatostatin analog: can be used to treat GH adenoma
Causes of hypopituitarism?
- Pituitary adenoma compression of normal tissue
- Apoplexy: bleeding of the adenoma
- Craniopharyngioma: kids
- Sheehan: infarct during pregnancy
Presentation of sheehan?
- Poor lactation
2. Loss of pubic hair
Functions of oxytocin?
- Uterine contraction
2. Release of breast milk with suckling
What is desmopressin?
ADH analog that can be used to treat diabetes insipidi s
**Think another name for ADH is vasopressin and desmopressin sounds like vasopressin
Drug that causes nephrogenic diabetes insipidus?
Think of all the people at FP who likely should be taking Li waiting in line to used the bathroom because they all have to be so bad
Tumor classically secreting ADH?
Small cell lung carcinoma
Drug causing SIADH?
Cyclophosphamide
Infx causing SIADH?
Pulmonary
Treatment of SIADH?
- Demeclocycline - ADH antagonist
What is lingual thyroid?
Thyroid stays at base of tongue and does not descend
Which way to lipids and sugars go in HYPERthyroid?
- HYPERglycemia
- HYPOcholesterolemia
Most common cause and pathology of PARAthyroid?
Graves: IgG stimulating TSH receptor
Why and when to exophthalmos and pretibial myxedema occur?
- Fibroblasts behind eye and on shin have TSH receptors that IgG is stimulating
- Leads to glycosaminoglycan release
What does “scalloping of the colloid” indicated?
Grave’s disease
Graves treatment?
- BBs: B1 is being over expressed
- Thioamide: blocks thyroid peroxidase
- Radioiodine ablation
What happens in organification?
Thyroglobulin combined with I2 in the follicle - this is catalyzed by peroxidase
Presentation of thyroid storm?
- Arrhythmia
- HYPERthermia - very high fever
- Vomiting / diarrhea
- Hypovolemic shock
- Agitation
6 Diaphoresis
**Most being caused by beta sympathetic stimulation
Treatment of thyroid storm?
- BB
- PTU
- Steroids
What does PTU do?
- Inhibits thyroid peroxidase
2. Inhibits peripheral conversion of T4 - T3
What is and multinodular goiter?
- Enlarged thyroid with many nodules
- Usually from iodine deficiency
- Usually non toxic - “euthyroid” but can become independent of TSH
What is cretinism?
CONGENITAL HYPOthyroidism in kids presenting with:
- Retardation - TH needed from brain / bones
- Short stature and skeletal abnormal
- Coarse facial features
- Enlarged tongue
- Umbilical hernia “potbelly”
- Jaundice at birth
Cretinism cause?
- Maternal HYPOthyroid
- Iodine deficiency
- Thyroid peroxidase deficiency
What is myxedema?
HYPOthyroid in adult:
- Myxedema of tissues
- Larynx: deepening of voice
- Tongue: enlarged tongue - Weakness
- Hypercholesterol
- Oligomenorrhea
Causes of myxedema?
- Hashimotos
- Iodine deficiency
- Lithium
- Amiodarone
What is Hashimoto’s thyroiditis?
- Autoimmune destruction of thyroid gland
- Associated with HLA-DR5
- Starts as HYPER and progresses to HYPO
- **Pernicious anemia seen in DR5 also
Markers for hashimoto?
- Antithyroglobulin Ig
- Antimicrosomal Ig
- Hurthle cells
What are the following indicative of?
- Antithyroglobulin Ig
- Antimicrosomal Ig
Hashimoto
When are hurthle cells seen?
Hashimoto
Progressive risk for hashimoto?
Marginal zone B cell lymphoma
What is subacute / de quervain / granulomatous thyroiditis?
- Granulomatous thyroiditis following viral infx
- Tender HYPERactive thyroid
- Self limited
When is thyroid tender?
“De Quervain, brings the pain”
Subacute / de quervain / granulomatous thyroiditis
What is reidel fibrosing thyroiditis?
- Chronic inflammation = fibrosis of thyroid
- HYPOThyroid
- ‘Hard as wood’ non tender thyroid
- Fibrosis can extend to airway
- Classically seen in younger females
What is a thyroid that is hard as wood and non tender indicative of?
Reidel fibrosing thyroiditis
Ddx for firm invading locally?
Older: anaplastic carcinoma
Young women:Reidel fibrosing thyroiditis
Iodine uptake study result in thyroid cancer?
Low
How is thyroid biopsied?
Fine needle aspiration
What is follicular adenoma?
- Benign tumor of thyroid glands
- Surrounded by capsule
- Usually not secreting TH
What is thyroid cancer surrounded by dense capsule indicative of?
Follicular adenoma
4 types of thyroid carcinoma?
- Papillary
- Follicular
- Medullary
- Anaplastic
Major risk factor for papillary carcinoma of thyroid?
- Ionizing radiation in childhood
Characteristics of papillary thyroid carcinoma?
- Orphan annie eye nuclei
- Nuclear grooves
- Psammoma bodies
Spread and prognosis of papillary thyroid cancer?
- Spread to cervical nodes with excellent prognosis
What is follicular carcinoma?
- Malignant proliferation of thyroid follicles
- Fibrous capsule with INVASION through capsule
Where does follicular carcinoma spread?
Hematogenously
What is medullary carcinoma?
- Malignancy of parafollicular C cells
- Produces lots of calcitonin = HYPO Ca
- Calcitonin can deposit in tumor = amyloid `
What thyroid tumor has amyloid?
Medullary thyroid carcinoma
When is hereditary thyroid carcinoma seen?
Medullary carcinoma of thyroid
- MEN2A and B
- RET mutations: detection warrants thyroidectomy
What is anaplastic carcinoma of thyroid?
- Malignant and undifferentiated
- Seen in elderly
- Poor prognosis
- Local invasion: dysphagia and respiratory compromise
Cell in parathyroid that releases PTH?
Chief cell
What does increased urinary cAMP indicate? How?
- Hyper PTH
- TPH binds GS activating adenylate cyclase
- AC converts ATP to cAMP
Not obvious lab findings in hyper PTH?
- Increased urinary cAMP
2. Increased alk phos: bone resorption from PTH turning on the osteoblasts
Most common cause of secondary hyper PTH?
- Renal failure increases PO4 in serum
- Excess P binds Ca increasing PTH
Genetic cause of HYPO PTH?
Digeorge from failure to develop 3 and 4th pharyngeal pouch
Presentation of HYPO PTH?
- Low PTH and Ca
- Muscle spasms: tetany
- Numbness and tingling
What is trousseau sign? Chvostek?
Signs of Hypo Ca:
Chvostek: tap on facial nerve = spasm
Trousseau: Fill BP cuff up = muscle spasms
What is pseudo HYPO PTH?
- End organs are not responding to PTH
- **Error in Gs protein
- Ca will be low but PTH will be elevated
What is the exocrine pancreas responsible for?
Digestive enzymes
Where are beta cells found?
Center of pancreatic islets of langerhorn
What type of hypersensitivity is TIDM and what is it associated with?
- Type IV - destruction by T lymphocytes
- HLA DR3 and 4
- Inflammation of islets with anti insulin Ig in blood
Presentation of TIDM?
- Weight loss
- Low muscle mass
- Polyphagia
- Polyuria / dipsia
- Glucosuria
Pathology of DKA?
- Increased stress = epinephrine increasing glucagon
- Glucagon increases lipolysis = increases FFAs
- Liver converts FFAs to ketone bodies
Type of acidosis in DKA?
Anion gap metabolic
K status in TIDM?
- No insulin so not being driven in cells
- High in blood put kidney wasting it so overall low
When are kussmaul respirations seen?
DKA - function is to blow off acid
Why is breath fruity in DKA?
Increased acetone in serum
Treatment of DKA?
- Fluids
- Insulin
- K
How is insulin resistance being caused in TIIDM?
Decreased # of insulin receptors on cell surfaces
Islet histology in TIIDM?
Amyloid
What is hyperosmolar nonketotic coma?
- Feared complication of TIIDM
- Glucose > 500 = deadly diuresis
- Leads to hypotension and coma in absence of ketones
3 manifestations of non enzymatic glycosylation seen in TIIDM?
- Large vessels: atherosclerosis
- Small: hyaline arteriolosclerosis
- RBC: increased HBA1C
Why and in what type of cells is osmotic damage seen in TIIDM?
Occurs in cells that don’t need insulin to take up glucose
- Schwann: neuropathy
- Pericytes of retinal blood vessels: hemmerhage = blind
- Lens: cataracts
Pathology of osmotic damage from glucose?
- Aldose reductase converts glucose to sorbitol
- Sorbitol pulls water in causing damage
What does gastrin cause in stomach?
“Zollinger ellison syndrome”
- Parietal cell production of Acid
- Multiple and extend to jejunum
What is ZE syndrome?
Gastrinoma creating treatment resistant peptic ulcers
What occurs in somatostatinoma?
- Achlorhydria: from gastrin inhibition
2. Cholelithiasis / steatorrhea: cck inhibition leading to inhibited gallbladder contraction
VIPoma presentation?
- Achlorhydria
- Watery diarrhea
- HYPO K
What catecholamines are secreted by the adrenal medulla?
- Epinephrine
2. Norepinephrine
Features of cushing’s?
- Muscle weakness and thin extremities
- Moon face, buffalo hump, truncal obesity
- Abdominal striae - impaired collagen
- HTN: upregulated A1
- Osteoporosis
- Immunosuppression
- Psychiatric changes
- Menstrual irregularities
Why does Cushing’s cause Muscle weakness and thin extremities?
- Cortisol wants to raise blood sugar and is breaking down muscle for gluconeogenesis
Why does cushing’s cause buffalo, moon, and central adiposity?
- Cortisol has raised blood sugar which is now being stored as fat in these locations
3 mechanisms of cortisol immunosuppression?
- Phospholipase A2 inhibition = no AA
- Inhibition of IL2 = T cell growth factor
- Inhibition of histamine from mast cells
Most common cause of cushing’s?
Exogenous, prescribed corticosteroids
Size of adrenals in exogenous cushing’s?
- Bilateral adrenal Atrophy
- High serum cortisol shuts down ACTH production in anterior pituitary
Size of adrenals in primary cushing’s?
- Adrenal that is producing will have HYPERplasia
- Adrenal NOT producing will shrink from diminished ACTH
Size of adrenals in secondary cushing’s?
“ACTH secreting adenoma”
- Both are hyperplastic
What 2 types of cushing’s is dexamethasone suppression test trying to distinguish?
- Primary pituitary ACTH secreting adenoma
2. Paraneoplastic ACTH secretion from another location
Cancer classically secreting paraneoplastic ACTH?
Small cell lung carcinoma
Interpretation of suppression test?
- Response seen: ACTH secreting pituitary adenoma
- Decreased cortisol levels will be seen - No response seen: Paraneoplastic ACTH
Aldosterone’s impact on distal collecting duct?
- Principal cell: grabs Na, dumps D
2. Alpha intercalated: dumps H ions
Renin levels in primary and secondary hyperaldosteron?
Primary: low, high aldosterone increase BP providing negative feedback to RAAS
What does fibromuscular dysplasia often do?
- Thickens renal artery decreasing flow to kidney activating RAAS
What is CAH?
“Congenital adrenal hyperplasia”
- Hyperplasia of BOTH adrenals
- Defect in enzyme needed for hormone production
- Cortisol is decreased so ACTH increased = HYPERplasia
Main fear of abrupt large decrease in cortisol?
- Life threatening HYPOtension from decrease in vascular tone
2 enzymes needed for mineralocorticoids and result of loss?
21 hydroxylase: zero mineralocorticoid activity
11 hydroxylase: If 21 functions, we have weak MCs but cannot be converted to final, STRONGER product
What cannot be made in 17 deficiency?
Cortisol AND sex steroids
Girls: delayed puberty
Boys: ambiguous genitalia
What is happening in waterhouse friderichsen?
N. meningitisis infx:
- DIC - from N. menin
- Bilateral adrenal necrosis - acute cortisol shortage
- Causes severe HYPOtension
3 causes of chronic adrenal deficiency?
- Autoimmune destruction
- TB
- Metastatic Cancer: Lung cancer
Presentation of adrenal insufficiency?
- HYPOtension and Na, HYPER K
- Weakness
- HYPERpigmentation
- vomit / diarrhea
Why does adrenal insufficiency cause HYPERpigmentation?
- No cortisol = increased ACTH
- ACTH is derived from POMC which also makes MSH “melanocyte stimulating hormone”
- Since you cannot make cortisol excess MSH is made
Type of cells in adrenal medulla?
Chromaffin cells derived from adrenal medulla
- Main source of catecholamines: NE/E
What is a pheochromocytoma?
- Tumor of chromaffin cells in adrenal medulla
Presentation of pheochromocytoma?
- Insane Episodic HTN > 200
- Beta causing heart to crank
- Alpha causing vessels to constrict - headaches, palpitations, tachy, sweet
2.
What are E and NE broken down into?
Epi: Metanephrine
Nor: Normetanephrine
***both metas broken down into HVA/VMA by MAO
Diagnosis of pheochromocytoma?
- Increased serum metanephrines
2. Increased urine meta and VMA
What do you need to do before removing pheochromocytoma?
Give phenoxybenzamine and BB: irreversible A blocker
- Want to make sure it is not spilling into blood when you excise tumor
- ***Need to give Phenoxy first as Beta is dilating so blocking first = 2x constriction
10% rule of pheochromocytoma?
10%:
- Familial
- Bilateral
- Malignant
- Outside adrenal medulla: bladder wall
* **Would present as HTN on urination
What is MEN2A?
- Medullary carcinoma thyroid
- Pheochromocytoma
- Parathyroid adenoma
* RET disease
What is MEN2B?
- Medullary carcinoma thyroid
- Pheochromocytoma
- Mucosol neuroganglioma
* RET disease
Pheochromocytoma associations?
- MEN2A
- MEN2B
- VHL
- NF type 1
What is cushing’s disease?
Refers specifically to syndrome caused by excess ACTH
When should cortisol be measured?
- Midnight, this is when it is lowest: rises and falls throughout day
- With tumor, might remain high at night
Cortisol levels with exogenous cortisol?
- Will actually show up as decreased as test is not picking them up natural axis is now depressed
GI symptoms of cortisol loss?
- Decreased catabolism: low serum nutrients
- GI distress
- Anorexia
* **Weight Loss, fatigue, HYPOglycemia
What is addison’s disease?
Chronic adrenal insufficiency
Another name for chronic adrenal insufficiency?
Addisons
What is a neuroendocrine cell?
Cell that receives synaptic signals from a neuron and responds by secreting hormones into serum
What is APUD + indicative of?
Neuroendocrine cells
What is a neuroblastoma?
- Tumor of adrenal medulla
- Classically in kid
What do suspect in 4 yo with abdominal mass crossing midline?
Neuroblastoma
Signs of neuroblastoma?
- Urine VMA / HVA
- Bombesin +
- Neuro specific enzyme +
- Homer wright rosettes
What is the following indicative of:
- Bombesin +
- Neuro specific enzyme +
- Homer wright rosettes
Neuroblastoma
Mutation in neuroblastoma?
nMYC
DDx for abdominal mass in kids?
- Wilms: renal tumor in > 10yo
- Smooth and dont cross midline - Neuroblastoma: adrenal tumor in
Different between pheo and neuroblastoma?
Pheo: mature secreting catecholamines
Neuroblastoma: immature, no secretion
What are VMA and HVA in urine indicative of?
Pheochromocytoma or neuroblastoma
Myxedema seen in HYPO or HYPER thyroid?
HYPO: it is actually sometimes referred to as myxedema
**However it is seen in graves but not other types of HYPER
Myopathies seen in hyper or HYPO thyroid?
Both
Best test for HYPO / HYPER?
Serum TSH
Why do thyroid issues impact menstruation?
TRH also stimulates prolactin which is a GnRH inhibitor
Why does lack of iodine lead to goiter?
- Without iodine, cannot make T3/4
- Pituitary over secretes TSH = HYPERplasia
When are anti TPO Igs seen?
Hashimotos
Do pretibial myxedema and exophthalmos present in thyroid tumors?
No, only in graves
Difference between iodine uptake in graves and toxic thyroid tumor?
Graves: diffuse uptake
Tumor: focal
Cold or hot thyroid nodules usually malignant?
Cold
Cancers presenting with psammoma bodies?
"PSAMM" Papillary thyroid Serous cyst.... Adenoma / carcinoma Meningioma Mesothelioma
What do recurrent laryngeal nerves innervated?
Larynx: vocal cords
What disease process can lead to Vitamin D induced HYPER Ca?
Granulomatous diseases: granulomas often have a-1-hydroxylase in them that is activating vitamin D
What is familial HYPOcalciuric HYPERcalcemia?
- High Ca is unable to inhibit PTH
- Decreased PO4, is still able to stop PTH
- Urine Ca is low
- Serum Ca is high
Symptoms of hyper PTH?
Usually Asymptomatic but if there are symptoms:
“Stones, Bones, abdominal groans (constipation), psychic overtones”
Kidneys handling of Ca / PO4 normally?
Ca resorber, P waster
When are shortened 4/5 digit seem?
- Pseudo HYPOparathyroidism
What does parathyroid adenoma do to PTH?
Increases
What happens to organs in acromegaly?
Organ hypertrophy
- Deep voice: laryngeal swelling
- Large tongue
- Colorectal polyps and cancer
- Cardiac hypertrophy
What happens in oral glucose test in acromegaly?
Normally glucose drops GH, will not happen in acromegaly
What is pegvisomant?
GH receptor antagonist
What is larone syndrome and what causes it?
Dwarfism caused by GH receptor malfunction
Presentation of dwarfism?
- Short limbs
- Small heads (achondroplasia is large head)
- Saddle nose
- Micropenis
What would labs be in dwarfism?
Elevated GH
Decreased IGF1
Drugs causing diabetes insipidus?
- Lithium (also causes hypothyroid)
2. Demeclocycline
Electrolyte changes in DI?
- High ca
2. Low K
Treatment for nephrogenic DI?
- Thiazide and K sparing diuretic
2. NSAIDs to decrease RBF
Most dangerous effect of hypotonic serum?
- Cerebral edema: fluid wants to move from veins to more hypertonic brain
What happens if you correct hypotonic serum too fust?
From low to high, the pons will die: “osmotic demyelination syndrome”
What is glucose converted to in the cells in which is causes osmotic damage?
Sorbitol
- This allows for more glucose to enter cell as [] gradient is not being changed
- Sorbitol is unable to leave cell without help of sorbitol dehydrogenase
- Sorbitol pulls water into cells leading to damage
Why does stress / illness precipitate DKA?
- These scenarios ramp up cortisol and epinephrine which are anti insulin hormones
When and why is kussmaul breathing seen?
DKA: deep and rapid breaths
- Body is acidotic so trying to blow off the extra CO2
First thing to give patient DKA?
- Fluids / saline
- Insulin
- K
What do nearly all neuroendocrine tumors respond well too?
Octreotide
Worst side effect of glucagonoma?
Necrolytic migratory erythema
What would a new onset diabetes and skin rash be indicative of?
Glucagonoma
Sequelae of insulinoma?
- Brain runs out of energy and shuts down leading to lethargy, coma, and death
What is carcinoid tumor?
- Neuroendocrine GI tract tumor secreting serotonin
- Only shows signs if in liver as liver metabolizes serotonin before it has effect if coming from stomach
Symptoms of carcinoid tumor?
- Asthma
- Diarrhea
- Flushing
- Right heart murmurs
- B3 deficiency that can cause pellagra: both are made from tryptophan
- So much Serotonin being made that none is left for B3
What is pelagra?
- Vitamin B3 deficiency that can be caused by carcinoid tumor presenting with:
1. Diarrhea
2. Dementia
3. Dermatitis
What to think if you see jejunal ulcers?
ZE syndrome as peptic ulcers usually dont make it this far down the stomach
Diagnosis of ZE syndrome?
Secretin test: normally this should decrease gastrin, but in ZE for some reason it increases
What happens in patient on BB who gets HYPOglycemia?
- Normal symptoms of HYPOglycemia are beta mediated hyper arousal, however BBs block these so they can pass out or get altered mental status as immediately
What occurs in M1?
3 Ps
- Pituitary tumors
- Parathyroid tumors
- Pancreas tumors
* Mutation in MEN bene
What occurs in MEN2A?
2Ms, 2Ps
- Marfanoid habitus
- Medullary thyroid carcinoma
- PTH tumors
- Pheochromocytoma
* RET gene mutation
What occurs in MEN2B?
3Ms, 1Ps
- Marfanoid habitus
- Medullary thyroid carcinoma
- Mucosal neuromas
- Pheochromocytoma
* RET gene mutation
How would addison’s disease impact a diabetic?
In addison’s, the adrenal is not producing cortisol which usually is insulin resistant. Since there is less cortisol in addison’s, this resistance is decreased leading to a lower required insulin load.
Injury to what causes chronic central DI?
- HYPOTHALAMIC nuclei: do not pick posterior pituitary as the hormones are made in hypo
- If damage is done to pituitary the axons will eventually regenerate allowing ADH secretion to resume
Signs of hyper Ca?
- Muscle weakness
- Constipation
- Mental status change
- Impaired urine [ ]
Treatment of CAH?
Low doses of corticosteroids to suppress the excess ACTH that is being secreted in its absence
What is proptosis?
Protrusion of the eyes
What medicine can cause syndrome looking like cushings?
HAART
Why would low levels of FSH lead to decreased spermatogenesis?
FSH is necessary to made androgen binding protein which keeps levels high in the testitcles and is necessary for sperm developent. If there are issues with FSH androgens will not be high enough for the development
Impact of sex hormones on growth places?
Initially encourage growth but will close plates during puberty
How do OCPs treat hirsutism?
The provide inhibition of LH which decreases androgen as well as increase SHBG which decreases free testosterone