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Day 4 > Endocrine - First Aid > Flashcards

Endocrine - First Aid Flashcards

1
Q

Most common ectopic thyroid tissue site is the _____. Removal may result in hypothyroidism if it is the only thyroid tissue present.

A

Tongue (Lingual Thyroid)

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2
Q

_____ presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs. persistent cervical sinus leading to branchial cleft cyst in lateral neck).

A

Thyroglossal Duct Cyst

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3
Q

Thyroid follicular cells are derived from the _____.

A

Endoderm

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4
Q

Thyroid parafollicular cells (a.k.a. C cells, produce Calcitonin) are derived from the _____.

A

Neural Crest

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5
Q

Adrenal Cortex and Medulla

A

GFR corresponds with Salt (mineralocorticoids), Sugar (glucocorticoids), and Sex (androgens).

The deeper you go, the sweeter it gets.

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6
Q

The adrenal cortex is derived from the _____.

A

Mesoderm

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7
Q

The medulla is derived from _____.

A

Neural Crest

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8
Q

The _____ secretes FSH, LH, ACTH, TSH, prolactin, GH, and β-endorphin. Derived from oral ectoderm (Rathke pouch).

A

Anterior Pituitary (Adenohypophysis)

FLAT PiG: FSH, LH, ACTH, TSH, PRL, GH

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9
Q

Melanotropin (MSH) is secreted from _____ of the pituitary.

A

Intermediate Lobe

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10
Q

Anterior Pituitary (Adenohypophysis):

hormone subunit common to TSH, LH, FSH, and hCG

A

α subunit

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11
Q

Anterior Pituitary (Adenohypophysis):

determines hormone specificity

A

β subunit

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12
Q

Anterior Pituitary (Adenohypophysis):

ACTH, MSH, and β-endorphin are derivatives of _____.

A

Proopiomelanocortin

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13
Q

Anterior Pituitary (Adenohypophysis):

Basophils secrete _____.

A

B-FLAT: Basophils—FSH, LH, ACTH, TSH

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14
Q

Anterior Pituitary (Adenohypophysis):

Acidophils secrete _____.

A
  • GH
  • PRL
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15
Q

The _____ stores and releases vasopressin (antidiuretic hormone, or ADH) and oxytocin.

A

Posterior Pituitary (Neurohypophysis)

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16
Q

Vasopressin (antidiuretic hormone, or ADH) and Oxytocin are made in the _____.

A

Hypothalamus (Supraoptic and Paraventricular Nuclei)

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17
Q

The posterior pituitary (neurohypophysis) derived from the _____.

A

Neuroectoderm

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18
Q

Endocrine Pancreas Cell Types

A

Islets of Langerhans are collections of α, β, and δ endocrine cells. Islets arise from pancreatic buds.

  • α = glucagon (peripheral)
  • β = insulin (central)
  • δ = somatostatin (interspersed)

Insulin is inside (β cells).

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19
Q

Insulin Synthesis

A

Preproinsulin (synthesized in RER) → cleavage of “presignal” → Proinsulin (stored in secretory granules) → cleavage of Proinsulin → exocytosis of Insulin and C-peptide equally

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20
Q

_____ are ↑ in insulinoma and sulfonylurea use, whereas exogenous insulin lacks _____.

A

C-Peptide

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21
Q

Insulin Function

A
  • Released from pancreatic β cells.
  • Binds insulin receptors (tyrosine kinase activity ①), inducing glucose uptake (carrier-mediated transport) into insulin-dependent tissue ② and gene transcription.
  • Unlike glucose, insulin does not cross placenta.
  • Brain utilizes glucose for metabolism but ketone bodies during starvation.
  • RBCs utilize glucose, as they lack mitochondria for aerobic metabolism.
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22
Q

Anabolic Effects of Insulin

A
  • ↑ glucose transport in skeletal muscle and adipose tissue
  • ↑ glycogen synthesis and storage
  • ↑ triglyceride synthesis
  • ↑ Na+ retention (kidneys)
  • ↑ protein synthesis (muscles)
  • ↑ cellular uptake of K+ and amino acids
  • ↓ glucagon release
  • ↓ lipolysis in adipose tissue
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23
Q

Insulin-Dependent Glucose Transporters

A

GLUT4: adipose tissue, striated muscle (exercise can also ↑ GLUT4 expression)

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24
Q

Insulin-Independent Transporters

A
  • GLUT1: RBCs, brain, cornea, placenta
  • GLUT2 (bidirectional): β islet cells, liver, kidney, small intestine
  • GLUT3: brain, placenta
  • GLUT5 (Fructose): spermatocytes, GI tract
  • SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine
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25
Q

Insulin-Independent Glucose Uptake

A

BRICK LIPS:

  • Brain
  • RBCs
  • Intestine
  • Cornea
  • Kidney
  • Liver
  • Islet (β) Cells
  • Placenta
  • Spermatocytes
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26
Q

Insulin Regulation

A
  • Glucose is the major regulator of insulin release
  • ↑ insulin response with oral vs. IV glucose due to incretins (eg. glucagon-like peptide 1 [GLP-1], glucose-dependent insulinotropic polypeptide [GIP]), which are released after meals and ↑ β cell sensitivity to glucose.
  • Release ↓ by α2, ↑ by β2 (2 = regulates insulin).
  • Glucose enters β cells ③ → ↑ ATP generated from glucose metabolism ④ closes K+ channels (target of sulfonylureas) ⑤ and depolarizes β cell membrane ⑥. Voltage-gated Ca2+ channels open → Ca2+ ⑦ influx and stimulation of insulin exocytosis ⑧.
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27
Q

Glucagon is made by the _____ and is secreted in response to hypoglycemia.

A

α Cells of the Pancreas

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28
Q

Glucagon promotes _____. It elevates blood sugar levels to maintain homeostasis when concentration of bloodstream glucose falls too low (ie. fasting state).

A
  • Glycogenolysis
  • Gluconeogenesis
  • Lipolysis
  • Ketone Production
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29
Q

Hypothalamic-Pituitary Hormones:

  • ↑ water permeability of distal convoluted tubule and collecting duct cells in kidney to ↑ water reabsorption
  • stimulus for secretion is ↑ plasma osmolality
A

ADH

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30
Q

Hypothalamic-Pituitary Hormones:

  • ↑ ACTH, MSH, β-endorphin
  • ↓ in chronic exogenous steroid use
A

CRH

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31
Q

Hypothalamic-Pituitary Hormones:

  • ↓ prolactin, TSH
  • antagonists (eg. antipsychotics) can cause galactorrhea due to hyperprolactinemia
A

Dopamine

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32
Q

Hypothalamic-Pituitary Hormones:

  • ↑ GH Analog (tesamorelin) used to treat
  • HIV‑associated lipodystrophy
A

GHRH

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33
Q

Hypothalamic-Pituitary Hormones:

  • ↑ FSH, LH
  • suppressed by hyperprolactinemia
  • tonic _____ suppresses HPG axis
  • pulsatile _____ leads to puberty and fertility
A

GnRH

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34
Q

Hypothalamic-Pituitary Hormones:

  • ↑ melanogenesis by melanocytes
  • causes hyperpigmentation in Cushing disease, as MSH and ACTH share the same precursor molecule, proopiomelanocortin
A

MSH

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35
Q

Hypothalamic-Pituitary Hormones:

  • causes uterine contractions during labor
  • responsible for milk letdown reflex in response to suckling
A

Oxytocin

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36
Q

Hypothalamic-Pituitary Hormones:

  • ↓ GnRH
  • pituitary prolactinoma → amenorrhea, osteoporosis, hypogonadism, galactorrhea
A

Prolactin

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37
Q

Hypothalamic-Pituitary Hormones:

  • ↓ GH, TSH
  • analogs used to treat acromegaly
A

Somatostatin

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38
Q

Hypothalamic-Pituitary Hormones:

  • ↑ TSH, prolactin
  • ↑ TRH (eg. in 1°/2° hypothyroidism) may increase prolactin secretion → galactorrhea
A

TRH

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39
Q

Prolactin is secreted mainly by the _____.

A

Anterior Pituitary

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40
Q

Prolactin is structurally homologous to _____.

A

Growth Hormone

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41
Q

_____ stimulates milk production in breast; inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release. Excessive amounts is associated with ↓ libido.

A

Prolactin

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42
Q

Prolactin Regulation

A
  • Prolactin secretion from anterior pituitary is tonically inhibited by dopamine from tuberoinfundibular pathway of hypothalamus.
  • Prolactin in turn inhibits its own secretion by ↑ dopamine synthesis and secretion from hypothalamus.
  • TRH ↑ prolactin secretion (eg. in 1° or 2° hypothyroidism).
  • Dopamine agonists (eg. bromocriptine) inhibit prolactin secretion and can be used in treatment of prolactinoma.
  • Dopamine antagonists (eg. most antipsychotics) and estrogens (eg. OCPs, pregnancy) stimulate
    prolactin secretion.
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43
Q

Growth Hormone (Somatotropin) is secreted by the _____.

A

Anterior Pituitary

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44
Q

_____ stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by
liver. It ↑ insulin resistance (diabetogenic).

A

Growth Hormone (Somatotropin)

Somatostatin keeps your growth static.
Somatomedin mediates your growth.

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45
Q

Growth Hormone (Somatotropin) Regulation

A
  • Released in pulses in response to growth hormone–releasing hormone (GHRH).
  • Secretion ↑ during exercise, deep sleep, puberty, hypoglycemia.
  • Secretion is inhibited by glucose and somatostatin release via negative feedback by somatomedin.
  • Excess secretion of GH (eg. pituitary adenoma) may cause acromegaly (adults) or gigantism (children).
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46
Q

Excess growth hormone (somatotropin) is treated with _____.

A

Somatostatin Analogs (eg. Octreotide)

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47
Q

Appetite Regulation:

  • stimulates hunger (orexigenic effect) and GH release (via GH secretagogue receptor)
  • produced by the stomach
  • sleep deprivation or Prader-Willi syndrome → ↑ production
  • acts via lateral area of hypothalamus to ↑ appetite (hunger center)
A

Ghrelin

Ghrelin makes you hunghr and ghrow.

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48
Q

Appetite Regulation:

  • satiety hormone
  • produced by adipose tissue
  • mutation of gene → congenital obesity
  • sleep deprivation or starvation → ↓ production
  • acts via ventromedial area of hypothalamus to ↓ appetite (satiety center)
A

Leptin

Leptin keeps you thin.

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49
Q

Appetite Regulation:

  • act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake → ↑ appetite
  • cause “the munchies”
A

Endocannabinoids

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50
Q

Antidiuretic Hormone (Vasopressin) is synthesized in the _____.

A

Hypothalamus (Supraoptic and Paraventricular Nuclei)

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51
Q

Antidiuretic Hormone (Vasopressin) is stored and secreted by the _____.

A

Posterior Pituitary

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52
Q

_____ regulates serum osmolality (V2-receptors) and blood pressure (V1-receptors). Primary function is serum osmolality regulation (↓ serum osmolality, ↑ urine osmolality) via regulation of aquaporin channel insertion in principal cells of renal collecting duct.

A

Antidiuretic Hormone (Vasopressin)

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53
Q

ADH level is ↓ in _____.

A

Central Diabetes Insipidus (DI)

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54
Q

ADH level is ↑ in _____.

A

Nephrogenic Diabetes Insipidus (DI)

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55
Q

Nephrogenic DI can be caused by mutation in _____.

A

V2-receptor

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56
Q

_____ is a treatment for central DI and nocturnal enuresis.

A

Desmopressin (ADH Analog)

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57
Q

Adrenal Steroids

A
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58
Q

Congenital Adrenal Hyperplasias

A
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59
Q

Congenital Adrenal Hyperplasias:

  • ↑ Mineralocorticoids
  • ↓ Cortisol
  • ↓ Sex Hormones
  • ↑ BP
  • ↓ K+
  • ↓ Androstenedione
  • XY: ambiguous genitalia, undescended testes
  • XX: lacks 2° sexual development
A

17α-Hydroxylase Deficiency

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60
Q

Congenital Adrenal Hyperplasias:

  • ↓ Mineralocorticoids
  • ↓ Cortisol
  • ↑ Sex Hormones
  • ↓ BP
  • ↑ K+
  • ↑ Renin activity
  • ↑ 17-Hydroxyprogesterone
  • most common
  • presents in infancy (salt wasting) or childhood (precocious puberty)
  • XX: virilization
A

21-Hydroxylase

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61
Q

Congenital Adrenal Hyperplasias:

  • ↓ Aldosterone
  • ↑ 11-Deoxycorticosterone (results in ↑ BP)
  • ↓ Cortisol
  • ↑ Sex Hormones
  • ↑ BP
  • ↓ K+
  • ↓ renin activity
  • XX: virilization
A

11β-Hydroxylase

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62
Q

Cortisol is formed in the _____.

A

Adrenal Zona Fasciculata

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63
Q

Cortisol Functions

A

Cortisol is a A BIG FIB:

  • ↑ Appetite
  • ↑ Blood pressure:
    • upregulates α1-receptors on arterioles → ↑ sensitivity to norepinephrine and epinephrine (permissive action)
    • at high concentrations, can bind to mineralocorticoid (aldosterone) receptors
  • ↑ Insulin resistance (diabetogenic)
  • ↑ Gluconeogenesis, lipolysis, and proteolysis (↓ glucose utilization)
  • ↓ Fibroblast activity (poor wound healing, ↓ collagen synthesis, ↑ striae)
  • ↓ Inflammatory and Immune responses:
    • inhibits production of leukotrienes and prostaglandins
    • inhibits WBC adhesion → neutrophilia
    • blocks histamine release from mast cells
    • eosinopenia, lymphopenia
    • blocks IL-2 production
  • ↓ Bone formation (↓ osteoblast activity)
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64
Q

Exogenous corticosteroids can cause reactivation of _____ (blocks IL-2 production).

A
  • TB
  • Candidiasis
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65
Q

Cortisol Regulation

A
  • CRH (Hypothalamus) stimulates ACTH release (Pituitary) → Cortisol production in Adrenal Zona Fasciculata.
  • Excess Cortisol ↓ CRH ACTH, and Cortisol secretion.
  • Chronic stress induces prolonged secretion.
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66
Q

Calcium Homeostasis

A
  • ↑ in pH → ↑ affinity of albumin (↑ negative charge) to bind Ca2+ → hypocalcemia (eg. cramps, pain, paresthesias, carpopedal spasm).
  • Ionized/free Ca2+ is 1° regulator of PTH; changes in pH alter PTH secretion, whereas changes in albumin do not.
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67
Q

Parathyroid Hormone is formed by the _____.

A

Chief Cells of Parathyroid

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68
Q

Parathyroid Hormone Functions

A
  • ↑ bone resorption of Ca2+ and PO43−
  • ↑ kidney reabsorption of Ca2+ in distal convoluted tubule
  • ↓ reabsorption of PO43− in proximal convoluted tubule
  • ↑ 1,25-(OH)2 D3 (Calcitriol) production by stimulating kidney 1α-hydroxylase in proximal convoluted tubule
  • PTH ↑ serum Ca2+, ↓ serum PO43–, ↑ urine PO43–, ↑ urine cAMP.
  • ↑ RANK-L (receptor activator of NF-κB ligand) secreted by osteoblasts and osteocytes.
  • Binds RANK (receptor) on osteoclasts and their precursors to stimulate osteoclasts and ↑ Ca2+ → bone resorption. Intermittent PTH release can also stimulate bone formation.

PTH = Phosphate-Trashing Hormone

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69
Q

_____ functions like PTH and is commonly increased in malignancies (eg. squamous cell carcinoma of the lung, renal cell carcinoma).

A

PTH-Related Peptide (PTHrP)

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70
Q

Parathyroid Hormone Regulation

A
  • ↓ serum Ca2+ → ↑ PTH secretion
  • ↑ serum PO43− → ↑ PTH secretion
  • ↓ serum Mg2+ → ↑ PTH secretion
  • ↓↓ serum Mg2+ → ↓ PTH secretion
  • Common causes of ↓ Mg2+ include diarrhea, aminoglycosides, diuretics, alcohol abuse.
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71
Q

Calcitonin is formed by the _____.

A

Parafollicular Cells (C Cells) of the Thyroid

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72
Q

_____ ↓ bone resorption of Ca2+.

A

Calcitonin

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73
Q

Calcitonin Regulation

A

↑ serum Ca2+ → Calcitonin secretion

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74
Q

Calcitonin opposes the actions of _____. Not important in normal Ca2+ homeostasis.

A

PTH

Calcitonin tones down serum Ca2+ levels and keeps it in bones.

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75
Q

Thyroid Hormone Production

A
  • Occurs in the follicles of the thyroid.
  • 5′-deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue (5-4-3).
  • Peripheral conversion is inhibited by glucocorticoids, β-blockers and propylthiouracil (PTU).
  • Functions of thyroid peroxidase include oxidation, organification of iodide and coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT).
  • Inhibited by PTU and methimazole.
  • DIT + DIT = T4
  • DIT + MIT = T3
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76
Q

_____ occurs when excess iodine temporarily ⊝ thyroid peroxidase → ↓ T3/T4 production.

A

Wolff-Chaikoff Effect

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77
Q

Signaling Pathways of Endocrine Hormones:

cAMP

A

FLAT ChAMP:

  • FSH
  • LH
  • ACTH
  • TSH
  • CRH
  • hCG
  • ADH (V2-receptor)
  • MSH
  • PTH
  • Calcitonin
  • GHRH
  • Glucagon
  • Histamine (H2-receptor)
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78
Q

Signaling Pathways of Endocrine Hormones:

cGMP

A

BAD GraMPa:

  • BNP
  • ANP
  • EDRF (NO)

*vasodilators

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79
Q

Signaling Pathways of Endocrine Hormones:

IP3

A

GOAT HAG:

  • GnRH
  • Oxytocin
  • ADH (V1-receptor)
  • TRH
  • Histamine (H1-receptor)
  • Angiotensin II
  • Gastrin
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80
Q

Signaling Pathways of Endocrine Hormones:

Intracellular Receptor

A

PET CAT on TV:

  • Progesterone
  • Estrogen
  • Testosterone
  • Cortisol
  • Aldosterone
  • T3/T4
  • Vitamin D
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81
Q

Signaling Pathways of Endocrine Hormones:

Receptor Tyrosine Kinase

A

Growth Factors:

  • Insulin
  • IGF-1
  • FGF
  • PDGF
  • EGF

*MAP kinase pathway

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82
Q

Signaling Pathways of Endocrine Hormones:

Nonreceptor Tyrosine Kinase

A

PIGGLET:

  • Prolactin
  • Immunomodulators (eg. cytokines IL-2, IL-6, IFN)
  • GH
  • G-CSF
  • Erythropoietin
  • Thrombopoietin

*JAK/STAT Pathway
*acidophils and cytokines

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83
Q

Signaling Pathways of Steroid Hormones

A
  • Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which ↑ their solubility.
  • In men, ↑ sex hormone–binding globulin (SHBG) lowers free testosterone → gynecomastia.
  • In women, ↓ SHBG raises free testosterone → hirsutism.
  • OCPs, pregnancy → ↑ SHBG
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84
Q

Cushing Syndrome ↑ Cortisol due to _____.

A
  • Exogenous Corticosteroids—result in ↓ ACTH, bilateral adrenal atrophy. Most common cause.
  • Primary Adrenal Adenoma, Hyperplasia, or Carcinoma—result in ↓ ACTH, atrophy ofuninvolved adrenal gland.
  • ACTH-Secreting Pituitary Adenoma (Cushing Disease); Paraneoplastic ACTH Secretion (eg. small cell lung cancer, bronchial carcinoids)—result in ↑ ACTH, bilateral adrenal hyperplasia. Cushing Disease is responsible for the majority of endogenous cases of Cushing Syndrome.
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85
Q

Findings in Cushing Syndrome

A
  • hypertension
  • weight gain
  • moon facies
  • abdominal striae
  • truncal obesity
  • buffalo hump
  • skin changes (eg. thinning, striae)
  • hirsutism
  • osteoporosis
  • hyperglycemia (insulin resistance)
  • amenorrhea
  • immunosuppression

*can also present with pseudohyperaldosteronism

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86
Q

Diagnosis of Cushing Syndrome

A

Screening Tests:

  • ↑ free cortisol on 24-hr urinalysis
  • ↑ midnight salivary cortisol
  • no suppression with overnight low-dose dexamethasone test

Serum ACTH:

  • If ↓, suspect adrenal tumor or exogenous glucocorticoids.
  • If ↑, distinguish between Cushing Disease and ectopic ACTH secretion (eg. from small cell lung cancer).
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87
Q

_____ is the inability of adrenal glands to generate enough glucocorticoids +/− mineralocorticoids for the body’s needs. Symptoms include weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances, sugar and/or salt cravings. Treatment glucocorticoid/mineralocorticoid replacement.

A

Adrenal Insufficiency

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88
Q

Diagnosis of Adrenal Insufficiency

A
  • Measurement of:
    • Serum Electrolytes
    • Morning/Random Serum Cortisol and ACTH (low cortisol, high ACTH in 1° adrenal insufficiency; low cortisol, low ACTH in 2°/3° adrenal insufficiency due to pituitary/hypothalamic disease)
    • ACTH Stimulation Test
  • Metyrapone Stimulation Test:
    • Metyrapone blocks last step of cortisol synthesis (11-deoxycortisol → cortisol).
    • Normal response is ↓ cortisol and compensatory ↑ ACTH and 11-deoxycortisol. In 1° adrenal insufficiency, ACTH is ↑ but 11-deoxycortisol remains ↓ after test.
    • In 2°/3° adrenal insufficiency, both ACTH and 11-deoxycortisol remain ↓ after test.
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89
Q

Adrenal Insufficiency:

  • deficiency of aldosterone and cortisol production due to loss of gland function → hypotension (hyponatremic volume contraction), hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation (due to ↑ MSH, a byproduct of ACTH production from proopiomelanocortin)
  • associated with autoimmune polyglandular syndromes
A

Primary Adrenal Insufficiency

Primary Pigments the skin/mucosa.

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90
Q

Adrenal Insufficiency:

  • sudden onset (eg. due to massive hemorrhage)
  • may present with shock in acute adrenal crisis
A

Acute Primary Adrenal Insufficiency

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91
Q

Adrenal Insufficiency:

  • due to adrenal atrophy or destruction by disease
  • autoimmune destruction most common in the Western world
  • TB most common in the developing world
A

Chronic Primary Adrenal Insufficiency

(Addison Disease)

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92
Q

_____ is acute 1° adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC, endotoxic shock.

A

Waterhouse-Friderichsen Syndrome

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93
Q

Adrenal Insufficiency:

  • seen with ↓ pituitary ACTH production
  • no skin/mucosal hyperpigmentation
  • no hyperkalemia (Aldosterone synthesis preserved due to intact Renin-Angiotensin-Aldosterone axis)
A

Secondary Adrenal Insufficiency

Secondary Spares the skin/mucosa.

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94
Q

Adrenal Insufficiency:

  • aeen in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal
  • Aldosterone synthesis unaffected
A

Tertiary Adrenal Insufficiency

Tertiary is from Treatment.

95
Q

_____ is the increased secretion of aldosterone from adrenal gland. Clinical features include hypertension,
↓ or normal K+, metabolic alkalosis.

A

Hyperaldosteronism

96
Q

Hyperaldosteronism:

  • seen with adrenal adenoma (Conn Syndrome) or bilateral adrenal hyperplasia
  • ↑ aldosterone, ↓ renin
  • causes resistant hypertension
A

Primary Hyperaldosteronism

97
Q

Hyperaldosteronism:

seen in patients with renovascular hypertension, juxtaglomerular cell tumors (renin-producing), and edema (eg. cirrhosis, heart failure, nephrotic syndrome

A

Secondary Hyperaldosteronism

98
Q

Most neuroendocrine tumors arise in the _____.

A

Top 3:

  • GI System (eg. carcinoid, gastrinoma)
  • Pancreas (eg. insulinoma, glucagonoma)
  • Lungs (eg. small cell carcinoma)

Others:

  • thyroid (eg. medullary carcinoma)
  • adrenals (eg. pheochromocytoma)
99
Q

Neuroendocrine Tumors:

  • most common tumor of the adrenal medulla in children, usually < 4 years old
  • originates from neural crest cells
  • occurs anywhere along the sympathetic chain
A

Neuroblastoma

100
Q

Neuroendocrine Tumors:

  • most common presentation is abdominal distension and a firm, irregular mass that can cross the midline (vs. Wilms tumor, which is smooth and unilateral)
  • less likely to develop hypertension than with Pheochromocytoma
  • can also present with Opsoclonus-Myoclonus Syndrome (“dancing eyes-dancing feet”)
A

Neuroblastoma

Neuroblastoma is Normotensive.

101
Q

Neuroendocrine Tumors:

  • ↑ HVA and VMA (catecholamine metabolites) in urine
  • Homer-Wright rosettes
  • Bombesin and NSE ⊕
  • associated with overexpression of N-myc oncogene
  • classified as an APUD tumor
A

Neuroblastoma

102
Q

Neuroendocrine Tumors:

  • most common tumor of the adrenal medulla in adults
  • derived from chromaffin cells (arise from neural crest)
  • may be associated with germline mutations (eg. NF-1, VHL, RET [MEN 2A, 2B])
A

Pheochromocytoma

Rule of 10’s:

  • 10% malignant
  • 10% bilateral
  • 10% extra-adrenal (eg. bladder wall, organ of Zuckerkandl)
  • 10% calcify
  • 10% kids
103
Q

Neuroendocrine Tumors:

  • most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension
  • may also secrete EPO → polycythemia
  • symptoms occur in “spells”—relapse and remit
A

Pheochromocytoma

Episodic Hyperadrenergic Symptoms (5 P’s):

  • Pressure (↑ BP)
  • Pain (headache)
  • Perspiration
  • Palpitations (tachycardia)
  • Pallor
104
Q

Neuroendocrine Tumors:

↑ catecholamines and catecholamine metabolites (eg. metanephrines) in urine and plasma

A

Pheochromocytoma

105
Q

Pheochromocytoma is treated with _____.

A
  • Irreversible α-antagonists (eg. phenoxybenzamine) followed by β-Blockers prior to tumor resection
  • α-blockade must be achieved before giving β-blockers to avoid a hypertensive crisis (A before B)
  • Phenoxybenzamine (16 letters) is given for Pheochromocytoma (also 16 letters)
106
Q

Neuroendocrine Tumors:

  • rare neuroendocrine tumor that secretes Vasoactive Intestinal Peptide (VIP)
  • most commonly arises in the pancreas
  • associated with MEN-1
  • primary symptom is secretory diarrhea
  • associated with WDHA (Watery Diarrhea, Hypokalemia, Achlorhydria) syndrome
A

VIPoma

107
Q

Skin/Hair Findings in Hypothyroidism

A
  • dry, cool skin (due to ↓ blood flow)
  • coarse, brittle hair
  • diffuse alopecia
  • brittle nail
  • puffy facies and generalized nonpitting edema (myxedema) due to ↑ GAGs in interstitial spaces → ↑ osmotic pressure → water retention
108
Q

Ocular Findings in Hypothyroidism

A

Periorbital Edema

109
Q

Muskuloskeletal Findings in Hypothyroidism

A
  • Hypothyroid Myopathy (proximal weakness, ↑ CK)
  • Carpal Tunnel Syndrome
  • Myoedema (small lump rising on the surface of a muscle when struck with a hammer)
110
Q

Laboratory Findings in Hypothyroidism

A
  • ↑ TSH (if 1°)
  • ↓ free T3 and T4
  • Hypercholesterolemia (due to ↓ LDL receptor expression)
111
Q

Skin/Hair Findings in Hyperthyroidism

A
  • warm, moist skin (due to vasodilation)
  • fine hair
  • onycholysis
  • pretibial myxedema in Graves disease
112
Q

Ocular Findings in Hyperthyroidism

A
  • ophthalmopathy in Graves disease (including periorbital edema, exophthalmos)
  • lid lag/retraction (↑ sympathetic stimulation of levator palpebrae superioris)
113
Q

Laboratory Findings in Hyperthyroidism

A
  • ↓ TSH (if 1°)
  • ↑ free T3 and T4
  • ↓ LDL, HDL, and total cholesterol
114
Q

Hypothyroidism:

  • most common cause of hypothyroidism in iodine-sufficient regions
  • autoimmune disorder with antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies
  • associated with HLADR3
  • ↑ risk of non-Hodgkin lymphoma (typically of B-cell origin)
  • may be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
  • Histology:
    • Hürthle cells
    • lymphoid aggregates with germinal centers
  • Findings:
    • moderately enlarged, nontender thyroid
A

Hashimoto Thyroiditis

115
Q

Hypothyroidism:

  • self-limited thyroiditis arising up to 1 year after delivery
  • presents as transient hyperthyroidism, hypothyroidism, or hyperthyroidism followed by hypothyroidism
  • majority of women are euthyroid following resolution
  • thyroid is usually painless and normal in size
  • Histology:
    • lymphocytic infiltrate with occasional germinal center formation
A

Postpartum Thyroiditis

116
Q

Hypothyroidism:

  • severe fetal hypothyroidism due to antibody-mediated maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis (most common cause in US), iodine deficiency, or dyshormonogenetic goiter
  • Findings:
    • pot-bellied
    • pale
    • puffy-faced
    • protruding umbilicus
    • protuberant tongue
    • poor brain development
A

Congenital Hypothyroidism (Cretinism)

6 P’s:

  • Pot-bellied
  • Pale
  • Puffy-faced
  • Protruding umbilicus
  • Protuberant tongue
  • Poor brain development
117
Q

Hypothyroidism:

  • self-limited disease often following a flu-like illness (eg. viral infection)
  • may be hyperthyroid early in course, followed by hypothyroidism (permanent in ~15% of cases)
  • Histology:
    • granulomatous inflammation
  • Findings:
    • ↑ ESR
    • jaw pain
    • very tender thyroid.
A

Subacute Granulomatous Thyroiditis (de Quervain)

De Quervain is associated with pain.

118
Q

Hypothyroidism:

  • thyroid is replaced by fibrous tissue with inflammatory infiltrate
  • fibrosis may extend to local structures (eg. trachea, esophagus), mimicking anaplastic carcinoma. 1⁄3 are hypothyroid
  • considered a manifestation of IgG4-related systemic disease (eg. autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis)
  • Findings:
    • fixed, hard (rock-like), painless goiter
A

Riedel Thyroiditis

119
Q

Causes of Hyperthyroidism

A
  • Graves Disease
  • Toxic Multinodular Goiter
  • Thyroid Storm
  • Jod-Basedow Phenomenon
120
Q

Hyperthyroidism:

  • most common cause of hyperthyroidism
  • thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse goiter) and dermal fibroblasts (pretibial myxedema)
  • infiltration of retroorbital space by activated T-cells → ↑ cytokines (eg. TNF-α, IFN-γ) → ↑ fibroblast secretion of hydrophilic GAGs → ↑ osmotic muscle swelling, muscle inflammation, and adipocyte count → exophthalmos
  • often presents during stress (eg. pregnancy)
  • associated with HLA-DR3 and HLA-B8
  • Histology:
    • tall, crowded follicular epithelial cells
    • scalloped colloid
A

Graves Disease

121
Q

Hyperthyroidism:

  • focal patches of hyperfunctioning follicular cells distended with colloid working independently of TSH (due to TSH receptor mutations in 60% of cases)
  • ↑ release of T3 and T4
  • hot nodules are rarely malignant
A

Toxic Multinodular Goiter

122
Q

Hyperthyroidism:

  • uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma, or surgery
  • presents with agitation, delirium, fever, diarrhea, coma, and tachyarrhythmia (cause of death)
  • may see ↑ LFTs
A

Thyroid Storm

Treat with the 4 P’s:

  • β-Blockers (eg. Propranolol)
  • Propylthiouracil
  • Corticosteroids (eg. Prednisolone)
  • Potassium iodide (Lugol iodine)
123
Q

Hyperthyroidism:

  • thyrotoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (eg. autonomous nodule) is made iodine replete
  • can happen after iodine IV contrast
  • opposite to Wolff-Chaikoff effect
A

Jod-Basedow Phenomenon

124
Q

Causes of Smooth/Diffuse Goiter

A
  • Graves Disease
  • Hashimoto Thyroiditis
  • Iodine Deficiency
  • TSH-Secreting Pituitary Adenoma
125
Q

Causes of Nodular Goiter

A
  • Toxic Multinodular Goiter
  • Thyroid Adenoma
  • Thyroid Cancer
  • Thyroid Cyst
126
Q

Thyroid Pathology:

  • benign solitary growth of the thyroid
  • most are nonfunctional (“cold”)
  • can rarely cause hyperthyroidism via autonomous thyroid hormone production (“hot” or “toxic”)
  • most common histology is follicular
  • absence of capsular or vascular invasion (unlike follicular carcinoma)
A

Thyroid Adenoma

127
Q

Thyroid Pathology:

  • typically diagnosed with fine needle aspiration
  • treated with thyroidectomy
  • complications of surgery include hoarseness (due to recurrent laryngeal nerve damage), hypocalcemia (due to removal of parathyroid glands), and transection of recurrent and superior laryngeal nerves (during ligation of inferior thyroid artery and superior laryngeal artery, leading to dysphagia, dysphonia)
A

Thyroid Cancer

128
Q

Thyroid Cancer:

  • most common, excellent prognosis
  • empty-appearing nuclei with central clearing (“Orphan Annie” eyes)
  • psammoma bodies
  • nuclear grooves
  • ↑ risk with RET/PTC rearrangements and BRAF mutations, childhood irradiation
A

Papillary Carcinoma

Papi and Moma adopted Orphan Annie.

129
Q

Thyroid Cancer:

  • good prognosis
  • invades thyroid capsule and vasculature (unlike follicular adenoma)
  • uniform follicles
  • hematogenous spread is common
  • associated with RAS mutation and PAX8-PPAR-γ translocations
A

Follicular Carcinoma

130
Q

Thyroid Cancer:

  • from parafollicular “C cells”
  • produces calcitonin
  • sheets of cells in an amyloid stroma (stains with Congo red)
  • associated with MEN 2A and 2B (RET mutations)
A

Medullary Carcinoma

131
Q

Thyroid Cancer:

  • older patients
  • invades local structures
  • very poor prognosis
A

Undifferentiated/Anaplastic Carcinoma

132
Q

Thyroid Cancer:

associated with Hashimoto thyroiditis

A

Lymphoma

133
Q

Diagnosing Parathyroid Disease

A
134
Q

_____ is due to accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome. It presents with tetany, hypocalcemia, and hyperphosphatemia.

A

Hypoparathyroidism

135
Q

tapping of facial nerve (tap the cheek) → contraction of facial muscles

A

Chvostek Sign

136
Q

occlusion of brachial artery with BP cuff (cuff the triceps) → carpal spasm

A

Trousseau Sign

137
Q

Hypoparathyroidism:

  • unresponsiveness of kidney to PTH → hypocalcemia despite ↑ PTH levels
  • presents as a constellation of physical findings known as _Albright Hereditary Osteodystroph_y:
    • shortened 4th/5th digits
    • short stature
    • obesity
    • developmental delay
  • autosomal dominant
  • due to defective Gs protein α-subunit causing end-organ resistance to PTH
  • defect must be inherited from mother due to imprinting
A

Pseudohypoparathyroidism Type 1A

138
Q

Hypoparathyroidism:

  • physical exam features of Albright Hereditary Osteodystrophy but without end-organ PTH resistance (PTH level normal)
  • occurs when defective Gs protein α-subunit is inherited from father
A

Pseudopseudohypoparathyroidism

139
Q

Hyperparathyroidism:

  • usually due to parathyroid adenoma or hyperplasia
  • hypercalcemia, hypercalciuria (renal stones), polyuria, hypophosphatemia, ↑ PTH, ↑ ALP, ↑ cAMP in urine
  • most often asymptomatic
  • may present with weakness and constipation, abdominal/flank pain (kidney stones, acute pancreatitis), neuropsychiatric disturbances
A

Primary Hyperparathyroidism

stones, thrones, bones, groans, and psychiatric overtones

  • hypercalciuria (renal stones)
  • polyuria (thrones)
  • Osteitis Fibrosa Cystica (bones)
  • weakness and constipation (“groans”)
  • neuropsychiatric disturbances (“psychiatric overtones”)
140
Q

_____ is characterized by cystic bone spaces
filled with brown fibrous tissue (“brown tumor” consisting of osteoclasts and deposited hemosiderin from hemorrhages; causes bone pain). Due to ↑ PTH, classically associated with 1° (but also seen with 2°) hyperparathyroidism.

A

Osteitis Fibrosa Cystica

141
Q

Hyperparathyroidism:

  • 2° hyperplasia due to ↓ Ca2+ absorption and/or ↑ PO43−
  • most often in chronic renal disease (causes hypovitaminosis D and hyperphosphatemia → ↓ Ca2+)
  • hypocalcemia, hyperphosphatemia in chronic renal failure (vs. hypophosphatemia with most other causes), ↑ ALP, ↑ PTH
A

Secondary Hyperparathyroidism

142
Q

Hyperparathyroidism:

  • refractory (autonomous) hyperparathyroidism resulting from chronic renal disease
  • ↑↑ PTH
  • ↑ Ca2+
A

Tertiary Hyperparathyroidism

143
Q

renal disease → 2° and 3° hyperparathyroidism → bone lesions

A

Renal Osteodystrophy

144
Q

_____ is caused by defective G-coupled Ca2+-sensing receptors in multiple tissues (eg. parathyroids, kidneys). Higher than normal Ca2+ levels required to suppress PTH. Excessive renal Ca2+ reuptake → mild hypercalcemia and hypocalciuria with normal to ↑ PTH levels.

A

Familial Hypocalciuric Hypercalcemia

145
Q

_____ causes enlargement of existing ACTH-secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease (due to removal of cortisol feedback mechanism). Presents with hyperpigmentation, headaches and bitemporal hemianopia. Treated with pituitary irradiation or surgical resection.

A

Nelson Syndrome

146
Q

Endocrine Pathologies:

  • excess GH in adults
  • typically caused by pituitary adenoma.
  • large tongue with deep furrows
  • deep voice
  • large hands and feet
  • coarsening of facial features with aging
  • frontal bossing
  • diaphoresis (excessive sweating)
  • impaired glucose tolerance (insulin resistance)
  • hypertension
  • ↑ risk of colorectal polyps and cancer
A

Acromegaly

147
Q

↑ GH in children → _____ (↑ linear bone
growth). HF most common cause of death.

A

Gigantism

148
Q

Endocrine Pathologies:

  • ↑ serum IGF-1
  • failure to suppress serum GH following oral glucose tolerance test
  • pituitary mass seen on brain MRI
A

Acromegaly

149
Q

Endocrine Pathologies:

  • treated with pituitary adenoma resection
  • if not cured, treat with Octreotide (Somatostatin analog) or Pegvisomant (growth hormone receptor antagonist), or Dopamine agonists (eg. Cabergoline).
A

Acromegaly

150
Q

_____ is caused by defective growth hormone receptors → ↓ linear growth (↑ GH, ↓ IGF-1). It presents with short height, small head circumference, characteristic facies with saddle nose and prominent forehead, delayed skeletal maturation, and small genitalia.

A

Laron Syndrome (Dwarfism)

151
Q

Endocrine Pathologies:

characterized by intense thirst and polyuria with inability to concentrate urine due to lack of ADH (central) or failure of response to circulating ADH (nephrogenic)

A

Diabetes Insipidus

152
Q

Diabetes Insipidus:

  • Etiology:
    • pituitary tumor
    • autoimmune
    • trauma
    • surgery
    • ischemic encephalopathy
    • idiopathic
  • Findings:
    • ↓ ADH
    • urine specific gravity < 1.006
    • serum osmolality > 290 mOsm/kg
    • hyperosmotic volume contraction
  • Water Deprivation Test:
    • > 50% ↑ in urine osmolality only after administration of ADH analog
  • Treatment:
    • Desmopressin
    • hydration
A

Central DI

153
Q

Diabetes Insipidus:

  • Etiology:
    • hereditary (ADH receptor mutation)
    • 2° to hypercalcemia
    • hypokalemia
    • lithium
    • Demeclocycline (ADH antagonist)
  • Findings:
    • normal or ↑ ADH levels
    • urine specific gravity < 1.006
    • serum osmolality > 290 mOsm/kg
    • hyperosmotic volume contraction
  • Water Deprivation Test:
    • minimal change in urine osmolality, even after administration of ADH analog
  • Treatment:
    • HCTZ
    • Indomethacin
    • Amiloride
    • hydration
    • dietary salt restriction
    • avoidance of offending agent
A

Nephrogenic DI

154
Q

Water Deprivation Test

A
  • No water intake for 2–3 hr followed by hourly measurements of urine volume and osmolality and plasma Na+ concentration and osmolality.
  • ADH analog (Desmopressin) is administered if serum osmolality > 295–300 mOsm/kg, plasma Na+ ≥ 145 mEq/L, or urine osmolality does not rise despite a rising plasma osmolality.
155
Q

Endocrine Pathologies:

  • excessive free water retention
  • euvolemic hyponatremia with continued urinary Na+ excretion
  • urine osmolality > serum osmolality
  • body responds to water retention with ↓ aldosterone and ↑ ANP and BNP → ↑ urinary Na+ secretion → normalization of extracellular fluid volume → euvolemic hyponatremia
  • very low serum Na+ levels can lead to cerebral edema, seizures
  • corrected slowly to prevent Osmotic Demyelination Syndrome (formerly known as Central Pontine Myelinolysis)
A

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

156
Q

Causes of SIADH

A
  • ectopic ADH (eg. small cell lung cancer)
  • CNS disorders/head trauma
  • pulmonary disease
  • drugs (eg. Cyclophosphamide)
157
Q

Treatment for SIADH

A
  • fluid restriction (first line)
  • salt tablets
  • IV hypertonic saline
  • diuretics
  • Conivaptan
  • Tolvaptan
  • Demeclocycline
158
Q

Increased urine osmolality during water deprivation test indicates _____.

A

Psychogenic Polydipsia

159
Q

Causes of Hypopituitarism

A
  • Nonsecreting Pituitary Adenoma
  • Craniopharyngioma
  • Sheehan Syndrome
    • ischemic infarct of pituitary following postpartum bleeding
    • pregnancy-induced pituitary growth → ↑ susceptibility to hypoperfusion
    • usually presents with failure to lactate, absent menstruation, and cold intolerance
  • Empty Sella Syndrome
    • atrophy or compression of pituitary (which lies in the sella turcica)
    • often idiopathic
    • common in obese women
    • associated with idiopathic intracranial hypertension
  • Pituitary Apoplexy
    • sudden hemorrhage of pituitary gland, often in the presence of an existing pituitary adenoma
    • usually presents with sudden onset severe headache, visual impairment (eg. bitemporal hemianopia, diplopia due to CN III palsy), and features of hypopituitarism
  • brain injury
  • radiation
160
Q

Treatment for Hypopituitarism

A

Hormone Replacement Therapy

  • corticosteroids
  • thyroxine
  • sex steroids
  • human growth hormone
161
Q

Acute Manifestations of Diabetes Mellitus

A
  • polydipsia
  • polyuria
  • polyphagia
  • weight loss
  • DKA (type 1)
  • hyperosmolar hyperglycemic state (type 2)

*Rarely, can be caused by unopposed secretion of GH and epinephrine. Also seen in patients on glucocorticoid therapy (steroid diabetes).

162
Q

Chronic Manifestations of Diabetes Mellitus

A
  • Nonenzymatic Glycation:
    • small vessel disease (diffuse thickening of basement membrane) → retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, neuropathy, nephropathy (nodular glomerulosclerosis, aka Kimmelstiel-Wilson nodules → progressive proteinuria [initially microalbuminuria; ACE inhibitors are renoprotective] and arteriolosclerosis → hypertension; both lead to chronic renal failure).
    • large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, gangrene → limb loss, cerebrovascular disease
    • MI is the most common cause of death.
  • Osmotic Damage (sorbitol accumulation in organs with aldose reductase and ↓ or absent sorbitol dehydrogenase):
    • neuropathy (motor, sensory [glove and stocking distribution], and autonomic degeneration)
    • cataracts
163
Q

Diagnosis of Diabetes Mellitus:

reflects average blood glucose over prior 3 months

A

HbA1c

  • cutoff: ≥ 6.5%
164
Q

Diagnosis of Diabetes Mellitus:

fasting for > 8 hours

A

Fasting Plasma Glucose

  • cutoff: ≥ 126 mg/dL
165
Q

Diagnosis of Diabetes Mellitus:

2 hours after consumption of 75g of glucose in water

A

2-Hour Oral Glucose Tolerance Test

  • cutoff: ≥ 200 mg/dL
166
Q

Diabetes Mellitus Type 1:

1° defect

A

autoimmune destruction of β cells (eg. due to glutamic acid decarboxylase antibodies)

167
Q

Diabetes Mellitus Type 1:

Insulin treatment

A

always

168
Q

Diabetes Mellitus Type 1:

age

A

< 30 y.o.

169
Q

Diabetes Mellitus Type 1:

obesity

A

no

170
Q

Diabetes Mellitus Type 1:

genetic predisposition

A
  • relatively weak (50% concordance in identical twins)
  • polygenic
171
Q

Diabetes Mellitus Type 1:

HLA system

A

Yes

  • HLA-DR4
  • HLA-DR3

4 – 3 = type 1

172
Q

Diabetes Mellitus Type 1:

insulin sensitivity

A

high

173
Q

Diabetes Mellitus Type 1:

ketoacidosis

A

common

174
Q

Diabetes Mellitus Type 1:

β-cells in islets

A

low

175
Q

Diabetes Mellitus Type 1:

serum insulin level

A

low

176
Q

Diabetes Mellitus Type 1:

classic symptoms of polyuria, polydipsia, polyphagia and weight loss

A

common

177
Q

Diabetes Mellitus Type 1:

histology

A

islet leukocytic infiltrate

178
Q

Diabetes Mellitus Type 2:

1° defect

A
  • ↑ resistance to insulin
  • progressive pancreatic β-cell failure
179
Q

Diabetes Mellitus Type 2:

genetic predisposition

A
  • relatively strong (90% concordance in identical twins)
  • polygenic
180
Q

Diabetes Mellitus Type 2:

HLA system

A

no

181
Q

Diabetes Mellitus Type 2:

insulin sensitivity

A

low

182
Q

Diabetes Mellitus Type 2:

ketoacidosis

A

rare

183
Q

Diabetes Mellitus Type 2:

β-cells in islets

A

variable (with amyloid deposits)

184
Q

Diabetes Mellitus Type 2:

serum insulin level

A

variable

185
Q

Diabetes Mellitus Type 2:

histology

A

islet amyloid polypeptide (IAPP) deposits

186
Q

Diabetes Mellitus:

  • one of the most feared complications of diabetes
  • usually due to insulin noncompliance or ↑ insulin requirements from ↑ stress (eg. infection)
  • excess fat breakdown and ↑ ketogenesis from ↑ free fatty acids, which are then made into ketone bodies (β-hydroxybutyrate > acetoacetate)
  • usually occurs in type 1 diabetes, as endogenous insulin in type 2 diabetes usually prevents lipolysis
A

Diabetic Ketoacidosis

187
Q

Signs and Symptoms of Diabetic Ketoacidosis

A

DKA is Deadly:

  • Delirium/psychosis
  • Kussmaul respirations (rapid, deep breathing)
  • Abdominal pain/nausea/vomiting
  • Dehydration
  • fruity breath odor (due to exhaled acetone)
188
Q

Laboratory Findings in Diabetic Ketoacidosis

A
  • hyperglycemia
  • ↑ H+
  • ↓ HCO3
  • ↑ anion gap metabolic acidosis
  • ↑ blood ketone levels
  • leukocytosis
  • hyperkalemia
    • depleted intracellular K+ due to transcellular shift from ↓ insulin and acidosis
  • osmotic diuresis → ↑ K+ loss in urine → total body K+ depletion
189
Q

Complications of Diabetic Ketoacidosis

A
  • life-threatening mucormycosis (usually caused by Rhizopus infection)
  • cerebral edema
  • cardiac arrhythmias
  • heart failure
190
Q

Treatment for Diabetic Ketoacidosis

A
  • IV fluids
  • IV insulin
  • K+ (to replete intracellular stores)
  • glucose if necessary to prevent hypoglycemia
191
Q

Diabetes Mellitus:

  • state of profound hyperglycemia-induced dehydration and ↑ serum osmolality, classically seen in elderly type 2 diabetics with limited ability to drink
  • hyperglycemia → excessive osmotic diuresis → dehydration
  • Symptoms:
    • thirst,
    • polyuria
    • lethargy
    • focal neurological deficits (eg. seizures)
    • can progress to coma and death if left untreated
  • Labs:
    • hyperglycemia (often > 600 mg/dL)
    • ↑ serum osmolality (> 320 mOsm/kg)
    • no acidosis (pH > 7.35, ketone production inhibited by presence of insulin)
  • Treatment:
    • aggressive IV fluids
    • insulin therapy
A

Hyperosmolar Hyperglycemic State

192
Q

Endocrine Pathologies:

  • tumor of pancreatic α cells → overproduction of glucagon
  • presents with dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight, depression
  • Treatment:
    • Octreotide
    • surgery
A

Glucagonoma

193
Q

Endocrine Pathologies:

  • tumor of pancreatic β cells → overproduction of insulin → hypoglycemia
  • Whipple Triad:
    • low blood glucose
    • symptoms of hypoglycemia (eg. lethargy, syncope, diplopia)
    • resolution of symptoms after normalization of glucose levels
  • symptomatic patients have ↓ blood glucose and ↑ C-peptide levels (vs. exogenous insulin use)
  • ∼ 10% of cases associated with MEN 1 syndrome
  • treated with surgical resection
A

Insulinoma

194
Q

Endocrine Pathologies:

  • tumor of pancreatic δ cells → overproduction of somatostatin → ↓ secretion of secretin, cholecystokinin, glucagon, insulin, gastrin, and gastric inhibitory peptide (GIP)
  • may present with diabetes/glucose intolerance, steatorrhea, gallstones, and achlorhydria
  • Treatment:
    • surgical resection
    • Somatostatin analogs (eg. Octreotide) for symptom control
A

Somatostatinoma

195
Q

Endocrine Pathologies:

  • most common malignancy in the small intestine
  • rare syndrome caused by carcinoid tumors (neuroendocrine cells with prominen rosettes), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT)
  • not seen if tumor is limited to GI tract (5-HT undergoes first-pass metabolism in liver)
  • results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right-sided valvular heart disease (tricuspid regurgitation, pulmonic stenosis) due to lung MAO-A enzymatic breakdown of 5-HT before left heart return
  • ↑ 5-hydroxyindoleacetic acid (5‑HIAA) in urine, niacin deficiency (pellagra)
  • associated with neuroendocrine tumor markers chromogranin A and synaptophysin
  • Treatment:
    • surgical resection
    • Somatostatin analog (eg. Octreotide)
A

Carcinoid Syndrome

Rule of 1/3s:

  • 1/3 metastasize
  • 1/3 present with 2nd malignancy
  • 1/3 are multiple
196
Q

Endocrine Pathologies:

  • gastrin-secreting tumor (gastrinoma) of pancreas or duodenum
  • acid hypersecretion causes recurrent ulcers in duodenum and jejunum
  • presents with abdominal pain (peptic ulcer disease, distal ulcers), and diarrhea (malabsorption)
  • positive secretin stimulation test—gastrin levels remain elevated after administration of secretin, which normally inhibits gastrin release
  • may be associated with MEN 1
A

Zollinger-Ellison Syndrome

197
Q

Multiple Endocrine Neoplasias have _____ inheritance.

A

Autosomal Dominant

All MEN are dominant (or so they think).

198
Q

Multiple Endocrine Neoplasias

A

MEN 1 = 3 P’s

  • Pituitary
  • Parathyroid
  • Pancreas

MEN 2A = 2 P’s

  • Parathyroid
  • Pheochromocytoma

MEN 2B = 1 P

  • Pheochromocytoma
199
Q

Multiple Endocrine Neoplasias:

  • pituitary tumors (prolactin or GH)
  • pancreatic endocrine tumors—Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare)
  • parathyroid adenomas
  • associated with mutation of MEN1 (menin, a tumor suppressor, chromosome 11), angiofibromas, collagenomas, and meningiomas
A

MEN 1

200
Q

Multiple Endocrine Neoplasias:

  • parathyroid hyperplasia
  • medullary thyroid carcinoma—neoplasm of parafollicular or C cells; secretes calcitonin; prophylactic thyroidectomy required
  • pheochromocytoma (secretes catecholamines)
  • associated with mutation in RET (codes for receptor tyrosine kinase) in cells of neural crest origin
A

MEN 2A

201
Q

Multiple Endocrine Neoplasias:

  • medullary thyroid carcinoma
  • pheochromocytoma
  • mucosal neuromas (oral/intestinal ganglioneuromatosis)
  • associated with marfanoid habitus
  • mutation in RET gene
A

MEN 2B

202
Q

Treatment for Type 1 DM

A

insulin replacement

203
Q

Treatment for Type 2 DM

A
  • oral agents (Metformin is first line)
  • non-insulin injectables
  • insulin replacement
  • weight loss is particularly helpful in lowering blood glucose
204
Q

Treatment for Gestational DM

A

insulin replacement if nutrition therapy and exercise alone fail

205
Q

Regular (short-acting) insulin is preferred for _____.

A
  • DKA (IV)
  • hyperkalemia (+ glucose)
  • stress hyperglycemia
206
Q

Diabetes Mellitus Management:

Injectables

A
  • Insulin Preparations
  • Amylin Analogs
  • GLP-1 Analogs
207
Q

Diabetes Mellitus Management:

Rapid Acting Insulin Preparations

A

1-hr peak, “no LAG”:

  • Lispro
  • Aspart
  • Glulisine
208
Q

Diabetes Mellitus Management:

Short Acting Insulin Preparations

A

2–3 hr peak: regular

209
Q

Diabetes Mellitus Management:

Intermediate Acting Insulin Preparations

A

4–10 hr peak: NPH

210
Q

Diabetes Mellitus Management:

Long Acting Insulin Preparations

A

no real peak:

  • Detemir
  • Glargine
211
Q

Diabetes Mellitus Management:

  • bind insulin receptor (tyrosine kinase activity)
  • Liver: ↑ glucose stored as glycogen
  • Muscle: ↑ glycogen, protein synthesis
  • Fat: ↑ TG storage
  • Cell Membrane: ↑ K+ uptake
  • can cause hypoglycemia, lipodystrophy, and rare hypersensitivity reactions
A

Insulin Preparations

212
Q

Diabetes Mellitus Management:

  • ↓ glucagon release
  • ↓ gastric emptying
  • ↑ satiety
  • can cause hypoglycemia (in setting of mistimed prandial insulin) and nausea
A

Amylin Analogs

  • Pramlintide
213
Q

Diabetes Mellitus Management:

  • ↓ glucagon release
  • ↓ gastric emptying
  • ↑ glucose-dependent insulin release
  • ↑ satiety
  • can cause nausea, vomiting, and pancreatitis
  • promotes weight loss (often desired)
A

GLP-1 Analogs

  • Exenatide
  • Liraglutide
214
Q

Diabetes Mellitus Management:

Oral Drugs

A
  • Biguanides
  • Sulfonylureas
  • Meglitinides
  • DPP-4 Inhibitors
  • Glitazones/Thiazolidinediones
  • Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
  • α-Glucosidase Inhibitors
215
Q

Diabetes Mellitus Management:

  • inhibit hepatic gluconeogenesis and the action of glucagon, by inhibiting mGPD
  • ↑ glycolysis and peripheral glucose uptake (↑ insulin sensitivity)
  • can cause GI upset, lactic acidosis (use with caution in renal insufficiency), and B12 deficiency
  • promotes weight loss (often desired)
A

Biguanides

  • Metformin
216
Q

Diabetes Mellitus Management:

  • close K+ channel in pancreatic β cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx
  • can cause hypoglycemia (↑ risk with renal failure) and weight gain
A

Sulfonylureas

  • 1st Generation :
    • causes disulfiram-like effects
    • Chlorpropamide
    • Tolbutamide
  • 2nd Generation:
    • causes hypoglycemia
    • Glimepiride
    • Glipizide
    • Glyburide
217
Q

Diabetes Mellitus Management:

  • close K+ channel in pancreatic β cell membrane → cell depolarizes → insulin release via ↑ Ca2+ influx (binding site differs from sulfonylureas)
  • can cause hypoglycemia (↑ risk with renal failure) and weight gain
A

Meglitinides

  • Nateglinide
  • Repaglinide
218
Q

Diabetes Mellitus Management:

  • inhibit DPP-4 enzyme that deactivates GLP-1
  • ↓ glucagon release and gastric emptying
  • ↑ glucose-dependent insulin release and satiety
  • causes mild urinary or respiratory infections
  • does not affect weight
A

DPP-4 Inhibitors

  • Linagliptin
  • Saxagliptin
  • Sitagliptin
219
Q

Diabetes Mellitus Management:

  • binds to PPAR-γ nuclear transcription regulator → ↑ insulin sensitivity and levels of adiponectin → regulation of glucose metabolism and fatty acid storage
  • causes weight gain, edema, HF, and ↑ risk of fractures
  • delayed onset of action (several weeks)
A

Glitazones/Thiazolidinediones

  • Pioglitazone
  • Rosiglitazone
220
Q

Diabetes Mellitus Management:

  • block reabsorption of glucose in proximal convoluted tubule
  • causes glucosuria, UTIs, vaginal yeast infections, hyperkalemia, dehydration (orthostatic hypotension), and weight loss
A

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

  • Canagliflozin
  • Dapagliflozin
  • Empagliflozin
221
Q

Diabetes Mellitus Management:

  • inhibit intestinal brush-border α-glucosidases → delayed carbohydrate hydrolysis and glucose absorption → ↓ postprandial hyperglycemia
  • can cause GI upset
  • not recommended if kidney function is impaired
A

α-Glucosidase Inhibitors

  • Acarbose
  • Miglitol
222
Q

Endocrine Drugs:

  • blocks thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis
  • used for hyperthyroidism
  • not used to treat Graves ophthalmopathy (treated with corticosteroids)
  • causes skin rash, agranulocytosis (rare), aplastic anemia, and hepatotoxicity
A

Thioamides

  • Propylthiouracil
  • Methimazole
223
Q

Endocrine Drugs:

  • blocks thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis
  • also blocks 5′-deiodinase → ↓ peripheral conversion of T4 to T3
  • used for hyperthyroidism
  • blocks peripheral conversion
  • used in first trimester of pregnancy (due to methimazole teratogenicity)
  • not used to treat Graves ophthalmopathy (treated with corticosteroids)
  • can cause kin rash, agranulocytosis (rare), aplastic anemia, and hepatotoxicity
A

Propylthiouracil

224
Q

Endocrine Drugs:

  • blocks thyroid peroxidase, inhibiting the oxidation of iodide and the organification and coupling of iodine → inhibition of thyroid hormone synthesis
  • used for hyperthyroidism
  • used in second and third trimesters of pregnancy (due to risk of PTU-induced hepatotoxicity)
  • not used to treat Graves ophthalmopathy (treated with corticosteroids)
  • causes skin rash, agranulocytosis (rare), aplastic anemia, and hepatotoxicity
  • possible teratogen (can cause aplasia cutis)
A

Methimazole

225
Q

Endocrine Drugs:

  • used in thyroid hormone replacement
  • used for hypothyroidism and myxedema
  • may be abused for weight loss
  • causes tachycardia, heat intolerance, tremors, and arrhythmias
A
  • Levothyroxine (T4)
  • Liothyronine (T3)
226
Q

Hypothalamic/Pituitary Drugs:

  • used in SIADH
  • blocks action of ADH at the V2-receptor
A

ADH Antagonists

  • Conivaptan
  • Tolvaptan
227
Q

Hypothalamic/Pituitary Drugs:

used in central DI, von Willebrand disease, sleep enuresis, and hemophilia A

A

Desmopressin

228
Q

Hypothalamic/Pituitary Drugs:

used in GH deficiency and Turner syndrome

A

GH

229
Q

Hypothalamic/Pituitary Drugs:

  • used in labor induction (stimulates uterine contractions)
  • facilitates milk letdown
  • controls uterine hemorrhage
A

Oxytocin

230
Q

Hypothalamic/Pituitary Drugs:

used in acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, and esophageal varices

A

Somatostatin (Octreotide)

231
Q

Endocrine Drugs:

  • ADH antagonist (member of tetracycline family)
  • used in SIADH
  • causes nephrogenic DI, photosensitivity, and abnormalities of bone and teeth
A

Demeclocycline

232
Q

Endocrine Drugs:

  • synthetic analog of aldosterone with little glucocorticoid effects
  • used in mineralocorticoid replacement in 1° adrenal insufficiency
  • adverse effects are similar to glucocorticoids; also edema, exacerbation of heart failure, and hyperpigmentation
A

Fludrocortisone

233
Q

Endocrine Drugs:

  • sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ → ↓ PTH
  • used in refractory hypercalcemia in 1° hyperparathyroidism, 2° hyperparathyroidism, or parathyroid carcinoma
  • causes hypocalcemia
A

Cinacalcet

234
Q

Endocrine Drugs:

  • nonabsorbable phosphate binder that prevents phosphate absorption from the GI tract
  • used in hyperphosphatemia in CKD
  • causes hypophosphatemia and GI upset
A

Sevelamer

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