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HRM > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

What are the discrete endocrine functional glands?

A

Pituitary, pineal, thyroid, parathyroid, adrenals

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2
Q

What are the glands with endocrine and exocrine function?

A

Kidney, pancreas, testes, ovaries, placenta

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3
Q

What type of tissue makes up the anterior lobe (adenohypophysis) of the pituitary?

A

Glandular epithelial tissue

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4
Q

What type of tissue makes up the posterior lobe (neurohypophysis) of the pituitary?

A

Neural secretory tissue

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5
Q

Functions of the pituitary gland photos/image

A
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6
Q

The anterior pituitary:

A

• receives Neurosecretory cell info from the ventral hypothalamus
• is composed of the pars distalis, intermedia, and tuberalis
• stains darkly

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7
Q

The posterior pituitary:

A
  • receives info from the paraventricular nucleus (oxytocin) and the supraoptic nucleus (ADH) of the hypothalamus
  • has the pars nervosa, and releases oxytocin/vasopressin
  • stains lightly
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8
Q

Anterior pituitary originates from where embryologically?

A

Oropharynx ectoderm via rathke’s pouch

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9
Q

Posterior pituitary derives from where embryologically?

A

Neuroectoderm via infundibular process

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10
Q

Components of the hypophysis (pituitary) and their derivation

Image/graph/table

A
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11
Q

What is the blood supply of the pituitary?

A
  1. Superior hypophyseal arteries from the internal carotid/posterior communicating artery of circle of Willis supplying the pars tuberalis, median eminence, infundibulum
  2. Inferior hypophyseal artery from the internal carotid arteries supplying the pars nervosa
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12
Q

What part of the pituitary gland has no direct arterial blood supply?

A

Anterior lobe: rather, supplied by superior hypophyseal artery —> portal veins —> secondary plexus of hypophyseal portal system

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13
Q

What layer of the pituitary gland contains large vesicles with colloid material?

A

Pars intermedia

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14
Q

Basophils and acidophils are found in what layer of the pituitary gland?

A

Pars distalis (stains darkly)

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15
Q

Chromophobes are found most commonly in what layer of the pituitary gland?

A

Pars intermedia

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16
Q

Pituicytes are found in what layer of the pituitary gland?

A

Pars nervosa— stand slightly, resembles neuronal tissue

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17
Q

What cells are the acidophils?

A

1. Somatotropes (GH, STH, acidophilic secretory vesicles)
2. Mammotropes (prolactin, acidophilic secretory vesicles, increase in pregnancy)

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18
Q

What cells are the basophils?

A
  1. Thyrotropes (TSH)
  2. Gonadotropes (FSH, LH, ICSH)
  3. Corticotropes (ACTH, MSH)
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19
Q

What is a Rathke cyst?

A

Remnants of a Rathke pouch. Follicles lined by cuboidal epithelium and filled with colloid. Found in the pars intermedia

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20
Q

What part of the pituitary gland encircles the infundibulum?

A

Pars tuberalis: highly vascularized area, superior hypophysis arteries terminate here to form the primary plexus of portal system — contains FSH, LH

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21
Q

The pars nervosa of the posterior pituitary contain neurosecretory vesicles that store what?

A

Oxytocin and vasopressin/ADH That can accumulate and dilated terminals (Herring bodies) adjacent to capillaries

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22
Q

Cell of the pars nervosa posterior pituitary image

A
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23
Q

What are the hypothalamic hormones that stimulate the anterior pituitary?

A
  1. Thyrotropin releasing hormone (TRH)
  2. Corticotropin releasing hormone (CRH)
  3. Gonadotropin releasing hormone (GnRH)
  4. Growth hormone releasing hormone (GHRH)
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24
Q

What are the hypothalamic hormones that inhibit the anterior pituitary?

A
  1. Dopamine (non-peptide)
  2. Somatostatin (growth hormone inhibiting hormone, GHIH)
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25
Q

Anterior pituitary hormone targets:

A

• GnRH —> FSH/LH —> ovary/testis
• GHRH —> GH —> liver/all tissue
• somatostatin —| GH
• TRH —> TSH —> thyroid
• TRH —> prolactin —> breast
• dopamine —| prolactin
• CRH —> ACTH —> adrenal cortex

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26
Q

What is thyroid stimulating hormone (TSH)?

A

• synthesis/secretion stimulated by TRH from hypothalamus
• stimulates growth of the thyroid gland and secretion of thyroid hormones such as T3 and T4

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27
Q

What is luteinizing hormone (LH)?

A

• synthesis/secretion stimulated by GnRH from the hypothalamus
• promotes estrogen/progesterone synthesis in ovaries and promotes testosterone synthesis in testes

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28
Q

What is follicle stimulating hormone (FSH)?

A

• synthesis/secretion stimulated by gonadotropin releasing hormone (GnRH) from hypothalamus
• stimulates follicle growth in ovaries and spermatogenesis in testes

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29
Q

What is adrenocorticotropin hormone (ACTH)?

A

• synthesis/secretion stimulated by corticotropin releasing hormone (CRH) in the hypothalamus
• stimulates corticosteroid production by the adrenal cortex (cortisol, etc.)

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30
Q

ACTH is synthesized from what?

A

Precursor polypeptide POMC (proopiomelanocortin)

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31
Q

What is present on ACTH N-terminus that can result in hyperpigmentation with excessive ACTH production?

A

Alpha-MSH (melanocyte-stimulating hormone)

~ this would be considered a secondary hypercortisolism

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32
Q

What is prolactin?

A

• structurally homologous to growth hormone, its secretion is under tonic inhibition by dopamine
• secretion stimulated by infant sucking and TRH
• promotes breast development, lactation, inhibits ovulation via inhibition of GnRH

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33
Q

What inhibits prolactin’s effect on lactation until birth?

A

Placental progesterone

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34
Q

What is a prolactinoma?

A

• most common functioning pituitary tumor leading to a hyper secretion of prolactin —> induces lactation, inhibits GnRH, decreases FSH and LH, leads to decreased progesterone/estrogen and testosterone —> amenorrhea, infertility, impotence, gynecomastia

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35
Q

What is the treatment for a prolactinoma?

A
  1. Dopamine agonist is the first line (bromocriptine, cabergoline) because it inhibits prolactin secretion
  2. Surgery due to increased to ICP/mass effect
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36
Q

What is growth hormone (GH) / somatropin/somatotropic hormone?

A

• structurally homologous to prolactin, the main function is to promote linear growth
• important in adolescence

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37
Q

What inhibits/stimulates growth hormone?

A

• stimulated by release of GHRH, exercise, trauma, and acute hypoglycemia
• inhibited by somatostatin
• decreased by age, disease, glucose

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38
Q

What does growth hormone stimulate the liver to produce?

A

insulin like growth factor-1
• increased protein synthesis, fat utilization
• decreased glucose uptake

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39
Q

What is released in response to hypoglycemia?

A

Growth hormone (GH)

• increases serum glucose levels by promoting glycogenolysis, gluconeogenesis, lipolysis, ketogenesis

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40
Q

Gigantism and acromegaly are diseases of what hormone?

A

growth hormone, GH

• gigantism: in children, acting on epiphyseal plate
• acromegaly: adults, acting on fused growth plate cartilage

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41
Q

What other conditions are gigantism and acromegaly associated with?

A

• enlarged liver and heart
• peripheral neuropathy secondary to nerve compression
• glucose intolerance and diabetes
• amenorrhea, impotence

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42
Q

What is the diagnosis of gigantism/acromegaly?

A

• increased serum IGF-1
• Oral glucose tolerance test fails to suppress GH

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43
Q

What are the treatments of acromegaly/gigantism

A

• surgical removal of pituitary
• octreotide: somatostatin analog
• bromocriptine: DA agonist
• pegvisomant: GH receptor antagonist

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44
Q

What are the functions of oxytocin?

A

• promotes contractions of the uterine myometrium during labor
• stimulates contractions of the mild epithelial cells in the breast (milk production)

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45
Q

What stimulates/inhibits oxytocin?

A

• stimulate: cervix dilation, suckling of infant
• inhibit: fear, pain, noise, fever

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46
Q

Diabetes insipidus is a defect in what?

A

Anti-diuretic hormone:

  1. Central DI: absent/insufficient ADH release (pituitary problem)
  2. Nephrogenic DI: normal ADH secretion, kidneys unresponsive (renal resistance)
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47
Q

What will a vasopressin challenge distinguish between?

A

Central DI and nephrogenic DI. Central DI will respond positively to the administration of vasopressin (Tx), and nephrogenic will not (needs thiazide diuretics)

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48
Q

What is SIADH?

A

Syndrome of inappropriate secretion of antidiuretic hormone: ADH in the absence of hyperosmolarity—> inability to dilute urine—> euvolemic hyponatremia

~ tx: water restriction

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49
Q

What drugs stimulate growth hormone, GH?

A
  1. Somatotropin: recombinant hGH
  2. Mecasermin: recombinant IGF-1
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50
Q

What medication’s decrease/inhibit growth hormone (GH)?

A
  1. Octreotide: somatostatin receptor agonist
  2. Pegvisomant: GH receptor antagonist
  3. Bromocriptine: dopamine D2 receptor agonist
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51
Q

What are the clinical applications of somatotropin?

A

• replacement in GH deficiency
• increased final adult height in children with conditions of short stature
• wasting associated with AIDS/malignancy
• short bowel syndrome

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52
Q

What are the side effects of somatotropin?

A

• edema
• hyperglycemia
• decreased insulin sensitivity
• thickening of bones, progression of scoliosis
• carpal tunnel syndrome

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53
Q

What are the clinical applications and side effects of Mecasermin?

A

• clinical application: replacement in IGF-I deficiency that is not responsive to somatotropin
• side effects: hypoglycemia, intracranial HTN, increased liver enzymes

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54
Q

What are the clinical applications of octreotide in the relation to growth hormone?

A

• acromegaly
• hormone secreting tumors
• acute control of bleeding from esophageal varices

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55
Q

What are the side effects of octreotide?

A

• GI disturbances
• gallstones
• bradycardia, cardiac arrhythmias
• thyroid disruption

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56
Q

What are the clinical applications and side effects of pegvisomant?

A

• clinical application: acromegaly
• side effects: minimal, liver enzyme increase on induction but not failure

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57
Q

What are the two effects that bromocriptine has?

A

Dopamine D2 receptor agonist suppresses pituitary secretion of:

  1. prolactin
  2. GH
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58
Q

What are the clinical applications of bromocriptine?

A

• GH based: acromegaly
• prolactin based: hyperprolactinemia

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59
Q

What are the side effects of bromocriptine?

A

• psychiatric disturbances, confusion
• G.I. disturbances
• orthostatic hypotension
• headache
• vasospasm

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60
Q

What is leuprolide?

A

• a GnRH analog that increases LH and FSH secretion with intermittent pulsatile administration (used for fertility)

• continuous non-pulsatile administration reduces LH and FSH secretion (endometriosis, precocious puberty, trans medicine)

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61
Q

What is the clinical application of oxytocin?

A

• induction and augmentation of labor
• control of uterine hemorrhage post delivery

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62
Q

What are the ADH V2 receptor agonist?

A

Desmopressin and vasopressin

~ used in central diabetes insipidus, hemophilia, and von Willebrand disease (Desmo)

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63
Q

What is the ADH receptor antagonist (V1a and V2 receptors)?

A

Conivaptan

~ typically used for hyponatremia stabilization in hospitalized patients (infusion only)

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64
Q

What tumors/diseases cause hyperpituitarism?

A

• adenoma (lactotroph, somatotroph, corticotrophin, gonadotroph)
• carcinoma
• genetics

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65
Q

What pituitary pathology causes hypopituitarism?

A

• apoplexy
• Sheehan
• empty sella
• hypothalamic
• inflammatory/infectious
• genetic

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66
Q

Mass effect of a pituitary disease typically affects what first?

A

Visual defects due to proximity of the optic chasm: bilateral temporal hemianopia

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67
Q

Lactotroph adenoma (prolactinoma)

A

• most common functioning adenoma
• secretes prolactin, stimulates breastmilk production, inhibits ovulation and spermatogenesis
• more commonly seen in women of reproductive years

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68
Q

Somatotroph adenoma

A

• excessive secretion of growth hormone, stimulation of hepatic secretion of insulin like growth factor-1 (IGF1)
• can cause gigantism, acromegaly, secondary diabetes mellitus
• tx: surgery, somatostatin analog (octreotide)

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69
Q

Corticotroph adenoma

A

• excess ACTH production leading to adrenal hyper secretion of cortisol, hypercortisolism, and cushing disease

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70
Q

Pituitary gland in Cushing disease

A

• highly basophilic/chromophobic
• positive ACTH immunohistochemistry
• densely granular EM
• crooke hyaline changes

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71
Q

Gonadotroph adenoma

A

• secretes hormones inefficiently/not at all (LH, FSH) leading to decrease energy/libido in men and amenorrhea in women from decreased LH

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72
Q

Thyrotroph adenoma

A

• a very rare, one percent of pituitary adenomas
• can cause hyper thyroidism by excessive TSH release

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73
Q

Non-functioning adenomas typically present with what finding?

A

Mass effect causing other brain injuries/symptoms. Hypopituitarism which may lead to pituitary apoplexy

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74
Q

What is the defining feature between a micro versus macroadenoma?

A

Macro is greater than 1 cm

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75
Q

Why does hypopituitarism occur?

A

• typically due to destructive processes such as tumors, trauma, subarachnoid hemorrhage, surgery, apoplexy, ischemia, TB/sarcoidosis

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76
Q

What is pituitary apoplexy?

A

• acute hemorrhage into the pituitary, often pre-existing adenoma
• sudden excruciating headache and diplopia, cardiovascular collapse, LOC, and death possible

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77
Q

What is Sheehan syndrome?

A

• postpartum pituitary necrosis
• anterior pituitary normally doubles and size during pregnancy without an increased blood supply from low pressure venous system (obstetric hemorrhage or shock may lead to infarction due to low blood supply)
• Posterior pituitary uninvolved due to separate arterial blood supply, eventually replaced by fibroid tissue or empty sella

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78
Q

What is primary empty sella syndrome?

A

• defect of the diaphragma sella allows arachnoid and CSF to herniate into the sella, compressing the pituitary
• most common in women with a history of multiple pregnancies
• results in visual defects, aberrant hyperprolactinemia

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79
Q

What is secondary empty sella syndrome?

A

• mass such as adenoma is surgically removed or infects lead to loss of function of the pituitary gland

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80
Q

What are the most common hypothalamic lesions?

A

• benign: craniopharyngioma
• metastatic tumors (breast, lung)
• radiation of other brain or nasopharyngeal areas

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81
Q

What are the common hypothalamic suprasellar tumors?

A

• gliomas (pilocytic astrocytoma, NF1)
• craniopharyngioma (Rathke pouch remnant)

~ slow growing, children typically have adamantinomatous type, adults have papillary type with calcification

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82
Q

What are the three components of an adamantinomatous type of a craniopharyngioma?

A
  1. Palisading epithelium
  2. Stellate reticulum
  3. Wet keratin
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83
Q

What are the gene mutations of adamantinomatous type of a craniopharyngioma?

A

Beta-Catenin and Wnt

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84
Q

What is the appearance of the papillary type of a craniopharyngioma?

A

Non-keratinizing squamous epithelium and capillary fibrovascular stroma

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85
Q

What is the mutation commonly associated with the papillary type of a craniopharyngioma?

A

BRAF V600E

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86
Q

What inflammatory/infectious properties can cause pituitary destruction and hypopituitarism?

A

• sarcoidosis
• tuberculosis
• meningitis

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87
Q

What is a genetic defect that can result in hypopituitarism, a defect of GH, prolactin, and TSH?

A

mutation of pituitary specific PIT-1 gene

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88
Q

GH deficiency in children causes what?

A

Pituitary dwarfism

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89
Q

Gonadotropin deficiency causes what?

A

Amenorrhea, infertility, decreased libido, impotence, loss of pubic and axillary hair

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90
Q

TSH deficiency causes what?

A

Hypothyroidism

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91
Q

ACTH deficiency causes what?

A

Hypoadrenalism

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92
Q

MSH (melanocyte stimulating hormone) deficiency results in what?

A

Color deficiency— pallor

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93
Q

What are the water soluble hormones?

A

• peptides
• proteins
• glycoproteins

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94
Q

What are the lipid soluble hormones?

A

• steroids
• thyroid hormone

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95
Q

Peptide hormone synthesis and processing: picture/flow chart/graph

A
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96
Q

What is unique about peptides/proteins/glycoprotein hormones?

A

• there are large protein molecules which dissolve well in the blood
• they are broken down quickly by peripheral enzyme systems
• bind surface membrane receptors and cause cellular response through signal transduction systems (secondary messenger systems that are fast, and gene transcription which is slow)

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97
Q

What is unique about lipid soluble hormones (steroids and cholesterol derived, and thyroid hormones)?

A

• lipophilic and easily cross membranes
• bind carrier proteins in order to travel in the blood, have a longer half-life
• cytoplasmic or nuclear receptors

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98
Q

What is the parent compound for all steroid hormones?

A

Cholesterol

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99
Q

Where in the body is norepinephrine turned into epinephrine?

A

In the adrenal medulla

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100
Q

Catecholamines (dopamine, norepinephrine, epinephrine) are _______ soluble

A

Water— even though they come from Tyrosine (like thyroid hormones that are lipid soluble)

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101
Q

What is a common carrier of steroid/TH hormones in the blood?

A

Albumin

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102
Q

Steroid hormones act primarily on (intracellular/extracellular) receptors

A

Intracellular receptors

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103
Q

What receptor is regulated in response to T3?

A

Beta adrenoreceptors (heart is more sensitive to catecholamines in the presence of thyroid hormone)

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104
Q

What receptor is down regulated with chronic stress?

A

Growth hormone (GH)

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105
Q

Hormone interactions: synergism, permissiveness, antagonism

A

Synergism: combined effect > sum of individually effects

Permissiveness: need second hormone to get full effect

Antagonism: one substance opposes the action of another

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106
Q

What are the three tiers of hypothalamic pituitary axis regulation?

A
  1. Hypothalamus (brain) releases hormones— GHRH, TRH, CRH, GnRH through portal system
  2. Pituitary secretes stimulating hormones— GH, TSH, ACTH, LH, FSH
  3. Peripheral target gland secrete peripheral hormones— IGF, thyroid hormone, cortisol, sex hormones
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107
Q

The secretion of peripheral hormones, causes what effect on the hypothalamus?

A

Negative feedback

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108
Q

What are the principal steroidogenic organs?

A
  1. Adrenal glands
  2. Gonads (ovaries, testes)
  3. Placenta
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109
Q

The body synthesizes cholesterol from what?

A
  1. De Novo via acetyl-CoA in the endoplasmic reticulum
  2. Uptake from dietary fat, lipoprotein particle
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110
Q

What are the steroid hormones?

A

Progesterone (intermediate of all), cortisol, corticosterone, aldosterone, testosterone, estradiol

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111
Q

What protein is required to transport cholesterol from the outer mitochondrial membrane to the mitochondrial matrix?

A

Steroid acute regulatory protein (StAR)

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112
Q

The rate limiting step in all steroids synthesis is what?

A

The conversion of cholesterol to pregnenolone by the mitochondrial matrix enzyme P450scc (CYP11A1)

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113
Q

What is Wolman disease?

A

Inherited mutations in lysosomal acid lipase (LAL). Characterized by cholesterol engorged macrophage infiltration of organs and death by organ failure in infancy

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114
Q

What is congenital lipoid adrenal hyperplasia?

A

• caused by mutation in StAR. Characterized by steroid hormone insufficiency resulting in female external genitalia and genetic XY individuals, salt wasting, and destruction of tissue due to fat accumulation

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115
Q

Wolman disease, lysosomal acid lipase deficiency, result in what liver findings?

A
  • liver steatosis
  • crystals of cholesterol esters in Kupffer cells
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116
Q

What is required to convert cholesterol to pregnonolone?

A

• CYP450scc (carbons are hydroxylated, bonds cleaved)
• 3 molecules of NADPH
• 3 molecules of oxygen

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117
Q

What part of the adrenal glands are catecholamines synthesized in? Steroids?

A

Catecholamines: adrenal medulla

Steroids: adrenal cortex

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118
Q

Region of the adrenal gland and its secretions

A

• determined by gradient of WNT/beta-catenin and cAMP/PKA

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119
Q

What is Addison’s disease?

A

• loss of adrenal function
• can be caused by TB/autoimmune reaction
• symptoms: fatigue, weight loss, hypotension, nausea, vomiting, hyperpigmentation due to increased ACTH activity in melanocytes

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120
Q

What is the most common cause of congenital adrenal hyperplasia?

A

Inherited mutations in P450c21 (CYP21) resulting in a less active enzyme (21 hydroxylase)—> this causes pregnonolone and progesterone to divert to androgen production

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121
Q

What are the symptoms of CYP21 mutated congenital adrenal hyperplasia? (21beta-hydroxylase deficiency)

A
  • decreased cortisol—> increased ACTH
  • decreased mineralcorticoids—> hypotension, hyponatremia, hyperkalemia
  • increased androgens—> early puberty, masculinization infemales
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122
Q

What are the symptoms of CYP17 mutated congenital adrenal hyperplasia? (17alpha-hydroxylase deficiency)

A

• decreased cortisol—> increased ACTH
• increased mineralocorticoids—> hypertension, hypokalemia
• decreased sex hormones—> XX, XY anatomically female without maturation

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123
Q

What are the symptoms of CYP11 mutated congenital adrenal hyperplasia? (11beta-hydroxylase deficiency)

A

• decreased cortisol —> increased ACTH
• increased 11 deoxycorticosterone—> hypertension
• increased sex hormones—> masculinization in females

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124
Q

What are the two cell types of the thyroid gland?

A
  1. Follicular/principal cells
  2. Parafollicular/C-cells
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125
Q

What are thyroid follicles?

A

• structural unit of thyroid
• simple epithelium: cuboidal, squamous, columnar depending on colloid/activate
• colloid contains a thyroglobulin (gel)

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126
Q

Explain the follicular/principal cells

A

• apical ends of cells adjacent to colloid, microvilli that extends into the colloid
• basal end of cells rest on basement membrane
• slightly basophilic cytoplasm, round nuclei, prominent nuclei
• synthesize thyroid hormones (T3, T4)

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127
Q

What is the difference between an inactive and an active follicular/principal cell?

A

• inactive: resting, basal level of thyroglobulin, squamous to cuboidal, few mitochondria/small Golgi, some rough ER

• active: stimulated by TSH from pituitary, columnar cells, numerous mitochondria/enlarged Golgi/increased rough ER, lipid droplets and PAS positive, releases T3 and T4 on basal surface

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128
Q

How does the thyroid gland change as it goes from inactive to active?

A

• lining endothelial cells go from squamous/flat to large columnar filled with colloid

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129
Q

What are parafollicular cells/C-cells?

A

• occurs singly or in small groups between follicular cells and membrane
• neuroendocrine cells that synthesize calcitonin

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130
Q

What cell is this?

A

Parafollicular thyroid gland cell

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131
Q

What does calcitonin (released by C-cells) do?

A

• lowers blood calcium by inhibiting bone resorption
• decreases osteoclast motility/numbers
• promotes excretion of calcium and phosphate from the kidneys

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132
Q

Where is thyroglobulin stored?

A

In colloid in the thyroid gland (glycoproteins and tyrosine residues available available for iodination—> T3 and T4 precursors)

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133
Q

How is T3/T4 created?

A

Iodine of thyroglobulin with tyrosine, stimulated by TSH produced by thyrotropes in the pars distalis of the pituitary

• 1tyrosine = monoiodotyrosine
• 2 tyrosine = diiodotyrosine

• 1 MIT + 1 DIT = T3
• 1 DIT + 1 DIT = T4

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134
Q

What are the two pathways for T3 and T4 production after endocytosis?

A

1. Lysosomal/physiologic: endosomes fuse with lysosomes,T3/T4 is released from Tg, active hormone T2/T4 diffuses through the cell and released at basal surface to capillaries

2. Transepithelial pathway: cell surface receptor megalin binds thyroglobulin and all allows it to skip the lysosome, iodinated thyroglobulin is released at the basal surface

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135
Q

What are the three types of cells of the parathyroid gland?

A
  1. Chief/principal cell
  2. Oxyphil cells
  3. Fat cells
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136
Q

What are the chief/principal cells of the parathyroid gland?

A

• small cells, most numerous, slightly acidophilic cytoplasm
• replicate when chronically stimulated by changes in blood calcium levels
• parathyroid hormone, PTH synthesis, storage and secretion to regulate circulating calcium

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137
Q

What is parathyroid hormone, and what does it stimulate?

A

• a peptide involved in the regulation of calcium and phosphate levels
• it increases blood calcium by stimulating osteoblasts to produce osteoclast stimulating factor (RANKL)—> bone resorption increases blood calcium

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138
Q

What are oxyphil cells of the parathyroid gland?

A

• larger than chief cells, smaller and dark staining nuclei with no known secretory function
• large eosinophilic cytoplasm that is finally granular due to numerous mitochondria

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139
Q

Where is the parathyroid gland developed from embryologically?

A

Derived from the pharyngeal endoderm of the the third and fourth pharyngeal pouch

~ principal cells differentiate first to regulate calcium, oxyphil cells differentiate at puberty

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140
Q

What is the pineal gland?

A

• a small pinecone shaped body with a Pia matter capsule attached by a stalk to the roof of third ventricle between the two hemispheres of the brain
• contains pinealocytes and interstitial (glial) cells

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141
Q

What are pinealocytes?

A

• majority (95%) of pineal gland cells
• resemble neuroendocrine cells
• produce melatonin at night

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142
Q

What are the interstitial (glial) cells of the pineal gland?

A

• Astrocytes (supportive role) similar to the pituicytes of the posterior pituitary

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143
Q

What is brain sand (corpora arenacea)?

A

• an area of the pineal gland that has concentrations of calcium phosphate and carbonate on carrier proteins
• accumulates with age, no known function
• use as a radiological marker because it is opaque on x-rays

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144
Q

Low light signals from the eye, induce what in the pineal gland?

A

Increase melatonin, reduced GnRH and GnIH, therefore reduced FSH, reduced LH

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145
Q

What alters emotional responses to changes in day length (seasonal effective disorder, Jetlag leg)?

A

The pineal gland

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146
Q

What is thyrotoxicosis?

A

Hyperthyroidism, a hypermetabolic state caused by excess circulating T3 and T4

• primary: excess production by the thyroid gland (most common)
• secondary: extrathyroid source

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147
Q

What is the most useful screening test for hyperthyroidism/thyrotoxicosis?

A

TSH level (will be low)

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148
Q

What are the three most common causes of hyperthyroidism?

A
  1. Diffuse hyperplasia, Graves’ disease
  2. Multinodular goiter
  3. Hyperfunctional adenoma
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149
Q

What are the clinical features of hyperthyroidism?

A

• hypermetabolic and increased sympathetic tone: warm, flushed skin, heat intolerance, increase sweating, weight loss despite increased appetite
• cardiac manifestations: increased cardiac contractility, tachycardia, palpitations, cardiomegaly, a fib, left ventricular dysfunction

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150
Q

What is Graves’ disease?

A
  • most common cause of endogenous hyperthyroidism: triad of thyroid toxicosis, ophthalmopathy, dermatopathy
  • autoimmune, secondary hypersensitivity reaction
  • glycosaminoglycan deposition in the ECM and lymphoid infiltrates
  • lab findings: high serum free T3/T4 and low TSH
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151
Q

Understanding thyroid function test: primary, secondary, hyperthyroidism, and T3 thyrotoxicosis

A
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152
Q

What are the treatments for Graves’ disease?

A
  • propylthiouracil: decrease synthesis of thyroid hormone (blocks T 4 5’ deiodinase)
  • radioiodine ablation
  • surgery for large goiters compressing adjacent structures
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153
Q

What is a goiter?

A

Thyroid enlargement and impaired synthesis of thyroid hormone, usually due to dietary iodine deficiency. Results in compensatory increase in TSH, causing hyperplasia and hypertrophy of follicular cells and gross enlargement of the gland

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154
Q

Where are goiters seen most commonly?

A

• endemic- where soil, food, water have low iodine
• sporadic- female predominance, puberty/young adults, unclear cause

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155
Q

What is hypothyroidism?

A

• decrease production of thyroid hormone, increased with age, more common in females
• primary: defect and thyroid gland (congenital, auto immune, iatrogenic)
• secondary: defect elsewhere in the axis (division of TSH, TRH)

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156
Q

What is congenital hypothyroidism?

A
  • hypothyroidism and infancy/early childhood typically in areas endemic of iodine deficiency, maternal hypothyroidism, agenesis, or dishormonogenic goiter
  • impaired skeletal and CNS development, short stature, coarse facial features, mental deficiency
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157
Q

Hypothyroidism in older children/adults is what?

A

Myxedema— general slowness, decreased metabolic rate. Caused by iodine deficiency, drugs (lithium), or thyroiditis

~ measuring TSH is the most sensitive screening test

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158
Q

Hashimoto thyroiditis:

A

• most common cause of hypothyroidism where iodine levels are sufficient
• autoimmune (autoantibodies to thyroglobulin and thyroid peroxidase) characterized by progressive gland destruction, Hurthle cell change, mononuclear infiltrates with germinal centers with or without fibrosis

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159
Q

What is subacute lymphocytic thyroiditis?

A

• painless, postpartum thyroiditis presenting with mild hyperthyroidism, goiter, or both
• autoimmune, circulating anti-thyroid peroxidase antibodies
• no hurthle cell metaplasia, otherwise similar to Hashimoto’s

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160
Q

What is subacute Granulomatous thyroiditis (De Quervain)?

A

• painful, age 40-50, women
• triggered by viral infection, Coxsackie, mumps, measles, adenovirus
• most common cause of thyroid pain, transient hyperthyroidism (high T3, T4 and low TSH) that is self limiting and normal function returns in 6-8 weeks

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161
Q

What is Riedel fibrosing thyroiditis- Woody thyroid?

A

• rare, fibrous disease causing thyroid gland hardening
• IgG4 related systemic disease
• clinical features: hard, immovable thyroid mass, hypothyroidism, compression effect (difficulty swallowing, breathing, voice changes)

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162
Q

What is a follicular adenoma (thyroid neoplasia)?

A

• discrete encapsulated solitary masses of follicular epithelium, typically non-functional
• GOF mutation in TSHR, GNAS
• rare: RAS or PIK3C a mutations or a PAX8-PPARG fusion gene

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163
Q

What does a thyroid follicular adenoma look like morphologically?

A

• gray/white two red/brown cut surface
• hemorrhage, fibrosis, calcification seen
• uniform small follicles with some colloid, follicle cell monotony, mitotic figures are rare

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164
Q

Microscopic examination for what must be done to exclude carcinoma when looking at thyroid adenoma?

A

Entire tumor capsule must be examined because capsular and vascular invasion define carcinoma

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165
Q

What does the Hurthle cell type look like in the transition from traditional cells in follicular adenoma?

A
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166
Q

What are the types of thyroid carcinoma?

A

• papillary, most common
• follicular
• anaplastic
• medullary

~ mutations in RET gene, or MEN2 are common genetic predispositions

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167
Q

Follicular thyroid carcinoma genetic mutation:

A

• women, 40-60
• acquired mutations that activate RAS or the PI3K/AKT arm of the receptor tyrosine kinase pathway (or LOF of PTEN)

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168
Q

Follicular thyroid carcinoma morphology

A

• gross: single nodule, gray to pink/tan to yellow with hemorrhage/necrosis occasionally
• microscopic: uniform cells forming small molecules, less colloid than normal, Hurthle variant occurs

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169
Q

What is the typical treatment of follicular thyroid carcinoma?

A

Although slowly enlarging painless mass, total thyroidectomy followed by radioactive iodine and thyroid hormone treatment to suppress endogenous TSH is the treatment

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170
Q

Papillary thyroid carcinoma gene mutations:

A
  • most common thyroid malignancy, 25-50 years old or childhood
  • exposure to ionizing radiation is a risk factor
  • GOF mutation of RET or NTRK1 receptor tyrosine kinase or BRAF
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171
Q

What does papillary thyroid carcinoma look like morphologically?

A

• gross: solitary/multifocal, cystic, fibrosis, calcification, papillae sometimes visible on surface
• microscopic: branching Papillae with fibrovascular core, clear ground glass nuclear appearance (orphan Annie eye), calcified psammoma bodies

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172
Q

What are the variant papillary thyroid carcinomas?

A

• Tall cell: older individuals, vascular invasion, BRAF, PTC/RET translocation
• diffuse sclerosing: younger age, papillary growth, squamous nest simulating Hashimoto, lymph involvement
• follicular variant: nuclear features of PTC but follicular architecture (can be infiltrative or encapsulated)

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173
Q

Anaplastic thyroid carcinoma gene mutations

A

• rare, high mortality undifferentiated tumor of thyroid epithelium, around 65
• RAS, PIK3CA mutations as well as TP53 in activation or activating beta-catenin

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174
Q

Medullary thyroid carcinoma:

A

• neuroendocrine neoplasm derived from parafollicular C- cells
• excessive secretion of calcitonin (occasionally also serotonin, ACTH, VIP) which can lead to neck masses/dysphasia/hoarseness, diarrhea (VIP), and Cushing (ACTH)

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175
Q

What are the gross and microscopic findings of medullary thyroid carcinoma?

A
  • gross: sporadic solitary nodule, familial may be bilateral or multicentric
  • microscopic: polygonal to spindle shaped cells, nests, tuberculae, c-cell hyperplasia
  • stromal amyloid may be seen
176
Q

Primary hyperparathyroidism is caused by what?

A

• autonomous overproduction of PTH
• adenoma or hyperplasia

177
Q

Secondary hyperparathyroidism is caused by what?

A

• compensatory hyper secretion of PTH in response to a prolonged hypocalcemia
• renal failure

178
Q

Tertiary hyperparathyroidism is caused by what?

A

• persistent secretion of PTH even after the cause of prolonged hypocalcemia is corrected
• renal failure followed by a transplant with continued high PTH

179
Q

What are the two established molecular defects for primary hyperparathyroidism?

A
  1. Cyclin D-1 inversions leading to the overexpression of cyclin D-1
  2. MEN-1 mutations
180
Q

Primary hyperparathyroidism from hyperplasia:

A

• sporadic or as a component of MEN syndrome
• diffuse or nodular increase in cellularity with decreased intervening fat, no atrophic suppressed rim of tissue— typically increased cellularity of the chief cells

181
Q

What is the essential criteria for determining parathyroid carcinoma?

A

• diffuse and pervasive marked atypia and increased mitotic activity
• invasion of surrounding tissues and metastasis

182
Q

What is the clinical course of primary hyperparathyroidism?

A

Typically asymptomatic, however can be symptomatic:

painful bones, renal stones, abdominal groans, and psychic moans

• osteoporosis, brown tumor, osteitis fibrosis cystica
• nephrolithiasis
• G.I. constipation, ulcer, pancreatitis, gallstone
• neuromuscular weakness
• aortic or mitral valve calcifications

183
Q

What is osteitis fibrosis cystica (von Recklinghausen disease)?

A

• conversion of compact cortical bone to cancellous bone by osteoclast forming cutting cones, dissecting osteitis

184
Q

What is a brown tumor of bone?

A

• associated with hyperparathyroidism
• can occur anywhere in the skeleton, non-specific pain/swelling
• one or more lytic lesions, many osteoclast-like giant cells

185
Q

Secondary hyperparathyroidism dominated by renal failure lead to what symptoms?

A

• mild skeletal abnormalities
• vascular calcification that can be life-threatening
• calciphylaxis skin/organ involvement
• cold necrotic plaque and eschar on abdomen/lower extremities

186
Q

What are the clinical features of hypoparathyroidism?

A

• tenany (neuromuscular irritability due to decreased calcium)
• mental status change
• intracranial calcification in the basal ganglia
• ocular calcification of the lens/cataract
• cardiovascular conduction defect/prolonged QT interval
• dental abnormalities, hypoplasia/failure of eruption/defective enamel

187
Q

Causes of hypercalcemia and PTH level graph/picture

A
188
Q

Graph comparing conditions with serum PTH, calcium, phosphate

A
189
Q

MEN1 (Wermer syndrome) deficits

A

• germline mutation in MEN one tumor suppressor gene menin—> block transcriptional activation by JunD
PPP
• parathyroid hyperplasia/adenoma
• pituitary tumors: prolactinoma
• pancreatic islet cell tumors: gastrinomas, insulinomas

190
Q

MEN2a

A

• germline GOF RET pro-oncogene, extracellular domain mutation
PPM
• pheochromocytoma
• medullary thyroid carcinoma
• parathyroid hyperplasia, hypercalciuria and renal stones

191
Q

MEN2b

A

• intracellular domain mutation
PMM
• pheochromocytoma
• medullary thyroid cancer, multifocal and more aggressive
• marfanoid habitus (neuromas or ganglion neuromas of skin, oral mucosa, eyes, respiratory, G.I.)

192
Q

Is it more important to undergo screening in MEN1 or MEN2?

A

• MEN2: routine genetic test for RET mutation. Undergo thyroidectomy if positive

193
Q

How does iodine enter the colloid of the thyroid gland?

A
  • iodine is uptaken and converted in the gut to iodide which is taken up by the thyroid gland
  • follicular cell via PENDRIN
  • undergoes oxidation to convert iodide to iodine
194
Q

How are T3 and T4 systemically transported?

A

• carried on proteins: thyroid binding globulin, transtryetin, albumin, lipoproteins

195
Q

How is T4 produced?

A

In the thyroid with iodine— conjugating thyroglobulin

196
Q

How is T3 produced?

A

In the thyroid gland AND in other tissues via T4,5’ deiodinase

• type 1: liver and kidney and thyroid (drug target)
• type 2: muscle, brain, pituitary, placenta, skin

197
Q

What is thyroid function good for in prenatal/infant/toddlers?

A

• bone growth and the closing of growth plates
• CNS development, primarily in the first trimester (no fetal production, supplementation from mom)

198
Q

What does thyroid function do in adults?

A

• heart: increases beta2 receptors (increased heart rate, contractility)
• lungs: stimulates respiratory centers
• skeletal muscle: promotes gluconeogenesis and lipolysis
• metabolism: increases O2 consumption

199
Q

What is the clinical presentation of primary hypothyroidism?

A

• bradycardia, weight gain, hair loss, decreased deep tendon reflexes, myalgia, increased depression

200
Q

When is it appropriate to screen a patient for primary hypothyroidism?

A

• obvious goiter
• hx head and neck surgery
• autoimmune disorders
• family history
• medication: lithium, amiodarone

201
Q

What are the lab value results of a patient with primary hypothyroidism?

A

• high TSH
• low total T3, low to normal T4

202
Q

Hashimoto’s (chronic autoimmune thyroiditis) causes what?

A

Primary hypothyroidism due to antibodies to thyroid peroxidase (TPO antibodies)

~ pt cannot make T3/T4 because they cannot add iodine to thyroglobulin

203
Q

What are the causes of secondary/central hypothyroidism?

A

• problem with the pituitary/hypothalamus—> no TRH/TSH
• strokes, postpartum Sheehan syndrome, radiation, surgeries

204
Q

What will the lab values show for a patient with secondary hypothyroidism?

A

TSH: low or normal (8% high)

Total T3: low or normal

Serum free T4: low or normal

205
Q

What is the treatment for hypothyroidism?

A

Levothyroxine: normalized TSH, alleviates symptoms. Must take on empty stomach (calcium, PPI, iron can bind it)

~ in pregnancy, increased dose 30 to 50% and check every 2 to 4 weeks

206
Q

What is the clinical presentation of hyperthyroidism?

A

• tachycardia, atrial fibrillation
• new or worsening hypertension
• weight loss
• diarrhea, diaphysis
• xalphthalmos (lid lag)

207
Q

What are the lab values for a patient with hyperthyroidism?

A

TSH: moderately decreased

T3: increased or normal

T4: increased or normal

208
Q

When diagnosing Graves’ disease without a classic presentation, what are the tests done?

A

• test for a thyrotropin receptor antibodies (TRAb)
• radioactive iodine uptake (entire gland lights up in Graves’ disease)
• ultrasonography for thyroidal blood flow

209
Q

If a patient has a painful thyroiditis, what is the common cause?

A

Granulomatous disease or infection

210
Q

If a patient has a non-painful thyroiditis, what is the common cause?

A

Drugs such as lithium, amiodarone or postpartum (17%)

211
Q

What are the pharmacological treatments of hyperthyroidism?

A
  1. Methanimazole: blocks thyroid peroxidase, cannot be used in pregnancy
  2. Propylthiouracil: blocks T4,5’ deiodinase
  3. Reactive iodine (can lead to hypothyroidism)
  4. Surgery- nodule removal
212
Q

What are the two targets of PTH?

A

Kidneys and bones. The goal is to increase serum calcium

213
Q

What are the effects of PTH on bone?

A

Acts on osteoblasts —> RANKL —> osteoclasts —> calcium and phosphorus release from bone

214
Q

What are the effects of PTH on the kidneys?

A
  • decreased Na-PO4 transporter in the proximal tubule
  • increased CaSR, and calcium absorption in the thick ascending limb
215
Q

What are the effects of PTH on the gut?

A

Indirect. PTH increases 1,25 dihydroxy Vit D leading to increased gut calcium absorption from food

216
Q

What is the effect of FGF-23 on the kidneys?

A

Stimulates PO4 excretion and blocks 1-alpha hydroxylase

217
Q

What are the lab values of primary hyperparathyroidism?

A

• elevated to PTH
• elevated calcium
• Elevated 24 hour urine calcium (>300mg)
• 1, 25 -OH can be normal or high

218
Q

What are the pharmacological treatments of primary hyperparathyroidism?

A
  1. cinecalcet (calcimimetic): blocks CaSR
  2. Bisphosphonates: inhibits osteoclasts

~ AVOID thiazides, high calcium diet

219
Q

What is familial hypocalciuric hypercalcemia?

A

• genetic disorder, FGF 23 mutation leading to an inactivation of the calcium sensing receptor (CaSR)

220
Q

What did the lab values show for familial hypocalciuric hypercalcemia?

A

PTH: increased

Vitamin D: normal, 1, 25-OH may be high

24 hour urine calcium: low

221
Q

What are the lab results of a patient with a malignancy of the parathyroid gland?

A

PTH: dramatically low, suppressed

Vitamin D : normal to low

PTHrP: parathyroid related peptide, mimics PTH, produced by some cancers. Can be increased or negative

222
Q

What are common cancers that produce PTHrP?

A

• squamous cell carcinoma
• renal cell carcinoma
• lung cancer
• ovarian cancer

~ multiple myeloma, and breast cancer can typically cause parathyroid hormone problems

223
Q

If a patient is having an acute hypercalcemia crisis (calcium > 14), what is the treatment?

A

• rehydrate
• calcitonin (increase renal excretion of calcium)
• furosemide (increase renal excretion of calcium)
• bisphosphonates: stabilized bone, may cause AKI, especially without fluids

224
Q

If a patient has high vitamin D elevation, what would the labs look like?

A

PTH: low

1,25-OH: normal to High

25-OH: normal to High

~ tx: discontinue supplementation

225
Q

What are the lab results for a patient with chronic granulomatous disease?

A

PTH: low

Vitamin D: very elevated 1, 25-OH

~ lithium, thiazides, excessive vitamin A may cause this

226
Q

What is the most common cause of secondary or tertiary hyperparathyroidism?

A

chronic kidney disease
• kidneys cannot filter, they cannot excrete what they do not see
• PTH: extremely elevated
• Phosphorus: extremely elevated
• GFR: low

~tx: phosphorus binders to be given with food to lower the absorption

227
Q

What medication can cause hypocalcemia with a low PTH (hypoparathyroidism)?

A

• bisphosphonates, citrates, calcium chelators, cisplatin, calcimimetics

228
Q

The cortex of the adrenal gland secretes what?

A

• steroids secretion (aldosterone, cortisol)
• partially regulated by anterior pituitary
• mesoderm derived

229
Q

The medulla of the adrenal gland secretes what?

A

• catecholamines (epi, NE)
• neural crest derived (ectoderm)

230
Q

What are the three layers of the adrenal cortex?

A
  1. Zona glomerulosa (secretes mineralocorticoids)
  2. Zona fasciculata (secretes glucocorticoids and gonadocorticoids)
  3. Zona reticularis (secretes glucocorticoids and gonadocorticoids)
231
Q

What is an easy way to remember the cortical zones of the adrenal gland and what each layer secretes?

A

“Go find Rex, make good sex”

232
Q

What adrenal gland cortex layer contains spongiocytes?

A

Zona fasciculata (broadest, middle zone that is lightly stained)

233
Q

What are the glucocorticoids produced by these on a fasciculata?

A

• cortisol
• hydrocortisone
• some androgens, very little estrogen

234
Q

What mineral corticoids are released by the Zona glomerulosa of the adrenal cortex?

A
  • aldosterone
  • deoxycortisone
235
Q

What sex steroids are produced by the Zona reticularis of the adrenal cortex?

A

• primarily androgens, very little estrogen

236
Q

The adrenal medulla is composed of what?

A

• chromaffin cells
• sinusoidal capillaries and nerves
• sympathetic nerve fibers terminate on chromaffin cells (release acetylcholine—> trigger granule release of epi, NE, chromogranins, ATP, and Ca2+)

237
Q

What are chromaffin cells in the adrenal medulla?

A

• modified postganglionic sympathetic neurons
• lack axons or dendrites
• neural crest origin
• innervated by Pre ganglionic sympathetics
• secrete direct directly into capillaries (instead of nerve terminals)

238
Q

Pheochromocytoma are tumors of what cells?

A

Chromaffin cells of the adrenal medulla

239
Q

Adrenal gland: factors that act on the gland and hormones that are secreted picture/graphic

A
240
Q

What is the blood supply to the adrenal gland?

A

• 3 suprarenal arteries
• three sets of capillaries: capsular plexus, cortical sinusoidal vessels, medullary capillaries

241
Q

How does adrenal blood supply return to the heart?

A

Capillary plexi —> medullary venules —> collecting veins —> medullary central vein —> suprarenal vein

242
Q

Islet of Langerhans of the pancreas are found more commonly in the (tail/head)?

A

Tail

243
Q

What is released by the pancreatic islet alpha cells?

A

• glucagon: polypeptide to raise blood sugar levels
• most numerous at the periphery of the islet

244
Q

What is released by the pancreatic islet beta cells?

A

• insulin to regulate protein, lower blood sugar levels
• c peptide
• amylin
• more numerous towards the center of the islet, can have crystalline appearance of secretory vesicles
• diseased = DM

245
Q

What is released by the pancreatic islet delta cells?

A

• somatostatin, a polypeptide with paracrine and endocrine effects (suppression of insulin and glucagon, reduces contractions of alimentary tract and gallbladder smooth muscles)

246
Q

What is released by the pancreatic islet gamma (F or PP) cells?

A

• pancreatic polypeptide with paracrine and endocrine effects (inhibits and somatic secretion from exocrine pancreas, relaxes gallbladder resulting in decreased bile secretion)
• predominant in the head of the pancreas

247
Q

What is produced by the pancreatic islet epsilon cells?

A

• Ghrelin, neuropeptide that regulates appetite (hunger hormone)

248
Q

What lab value is an extremely specific marker for functioning thyroid tissue?

A

Thyroglobulin: it is only produced by thyroid tissue

249
Q

Anti-thyroid peroxidase antibodies are most sensitive and specific for what disease?

A

Hashimoto thyroiditis (can also rarely be presented in Graves’ disease)

250
Q

Anti-TSH receptor antibodies are seen in patients with history of/who currently have what disease?

A

Graves’ disease

251
Q

What’s the difference in a radioactive iodine uptake exam for Graves’ disease versus Hashimoto thyroiditis?

A

• graves: RAIU is elevated, the entire gland becomes “hot”
• Hashimoto’s: uptake is usually low, with patchy hotspots in the gland

252
Q

When a radioactive iodine uptake test shows cold nodules in the thyroid, what does this indicate?

A

Cancer/malignancy

253
Q

Low TSH and a high T4 indicates what?

A

Primary hyperthyroidism

254
Q

High TSH and low T4 indicates what?

A

Primary hypothyroidism

255
Q

Low TSH and a low T4 indicates what?

A

Secondary hypothyroidism

256
Q

High T4 and a normal- high TSH indicates what?

A

Secondary (or tertiary) hyperthyroidism

257
Q

What’s the most common cause of a tertiary hyperthyroidism?

A

Problem with the hypothalamus: TRH producing adenoma

258
Q

Postpartum thyroiditis is most similar to what type of thyroiditis?

A

Hashimoto’s (including anti-thyroid peroxidase antibodies)

However:
1/3 of patients will have hyperthyroidism and hypothyroidism, 1/3 will have only hypothyroidism, 1/3 will have only hypothyroidism

259
Q

What are the treatments of postpartum thyroiditis?

A

• beta blockers (propanolol)
• levothyroxine in the hypothyroidism state

~ hyperthyroidism is typically self limited

260
Q

Postpartum depression typically starts when?

A

1-3 weeks following delivery, with symptoms including strong feelings of sadness, anxiety, despair. Having trouble coping with daily tasks, treatment and counseling recommended

261
Q

What causes and/or contributes to the development of postpartum depression?

A

• drastic changes in hormone levels
• hx of depression
• emotional factors relating to pregnancy/delivery
• fatigue and lifestyle choices

262
Q

Short term stress responses are mediated by what?

A

The adrenal medulla

263
Q

Prolonged stress responses are mediated by what?

A

The adrenal cortex

264
Q

Unlike mineralocorticoids and androgens, glucocorticoids can bind to multiple receptors, Including:

A

Glucocorticoid receptors and mineralocorticoid receptors

265
Q

The rate limiting step in adrenal steroids synthesis is:

A

Cholesterol to pregnenolone via cholesterol demolase/P450scc/ CYP11A1

266
Q

What can stimulate CRH in the hypothalamus?

A

Circadian rhythm and stress

267
Q

Tissue location of what defines activity or inactivity of glucocorticoid metabolism?

A

11beta-hydroxysteroid dehydrogenase type 1 and type 2

268
Q

What is the metabolic effect of cortisol?

A

Cortisol effectively increases blood glucose concentration

269
Q

The rate of secretion of aldosterone (mineralocorticoid) is dependent on what?

A

Rate of secretion adjusted depending on extracellular volume, [K+], [Na+], and arterial pressure

~ high serum K increases secretion, high serum Nadecreases secretion, RAAS system increases secretion

270
Q

Does aldosterone have a feedback mechanism on ACTH?

A

No

271
Q

Where are mineralocorticoid receptors present?

A

Kidney, colon, sweat glands, heart, hippocampus, brown adipose

272
Q

Mineralocorticoid receptor has equal affinity for mineralocorticoid and glucocorticoid (aldosterone and cortisol). What differentiates the response that occurs?

A

11beta-HSD2 allows for specificity of mineralocorticoid receptor responding to MC

273
Q

What are the roles of adrenal androgens during development (DHEA, DHEAS, androstenedione)

A

• fetal development
• adrenarche
• adult: maintain female axillary and pubic hair, contributory to female testosterone more than male
• menopause

274
Q

What are the common causes of Cushing syndrome?

A

Glucocorticoid therapy (iatrogenic), and primary glandular excess production of cortisol (adrenal tumors)

275
Q

What is a common cause of primary hyperaldosteronism?

A

Conn syndrome: benign adenoma in the Zona glomerulosa —> excess aldosterone and increased sodium reabsorption and potassium secretion

276
Q

What is Addison’s disease?

A

• primary adrenal insufficiency
• idiopathic atrophy of the adrenal cortex, can be caused by autoimmune process, TB, AIDS

277
Q

What are the two most common causes of congenital adrenal hyperplasia?

A

• 21- hydroxylase deficiency
• 11beta- hydroxylase deficiency

~ autosomal recessive disorders causing cortisol deficiency, increased ACTH and bilateral adrenal gland hyperplasia result

278
Q

What is the difference between synthetic glucocorticoids and natural?

A

• increase glucocorticoid potency (ratio of GCR to MCR effect)
• less protein bound, slower metabolism

279
Q

Why do glucocorticoid treatments have anti-inflammatory effects?

A

• They decrease arachidonic acid metabolites (leukotriene, prostaglandins, prostacyclins)
• inhibition of phospholipase A2
• repression of COX2 expression
• inhibition of NFkB

280
Q

Why do glucocorticoid treatments work as immunosuppressants for organ transplant patients?

A

• Broadly immunosuppressive
• inhibit inflammation that occurs at the boundary of donated tissue
• inhibits antigen release from the grafted/donor tissue
• SE: increase susceptibility to infection

281
Q

Why do glucocorticoid treatments have an anti-allergy effect?

A

They inhibit the synthesis of histamine by mast cells, limiting the duration of an allergy attack

282
Q

What are the side effects of glucocorticoid treatment?

A

• hyperglycemia
• infection
• cardiac: increased to contractility, increased blood pressure, increased sodium and water retention
• CNS: lowers seizure threshold, behavioral changes (mood depression, elevation, anxiety/psychosis)

283
Q

What do glucocorticoids do on the G.I. system?

A

The inhibition of prostaglandin and prostacyclin increase the gastric acid and pepsin secretion. May suppress local immune response to H. pylori

284
Q

What is the effective glucocorticoids on bone metabolism?

A

Direct inhibition of osteoblasts —> secondary stimulation of PTH which stimulates osteoclasts —> osteoporosis risk

285
Q

What is Ketoconazole?

A

• inhibits side chain cleavage (P450scc) and other CYP enzymes used for Cushing syndrome/hypercortisolism

286
Q

What are etomidate and metyrapone?

A

• inhibit 11beta-hydroxylase interfering with cortisol and corticosterone (and therefore aldosterone) production. Used for the treatment of Cushing syndrome/hypercortisolism

287
Q

What are new targets for pituitary adenomas that secrete ACTH and lead to Cushing syndrome/hypercortisolism?

A

• somatostatin analog: pasireotide
• D2 agonist: cabergoline, bromocriptine
• GR antagonist: mifepristone

288
Q

What are the HPA function tests for hypocortisolism/adrenalism?

A

• 24 hour urine free cortisol
• ACTH stimulation (short test to confirm low cortisol post stimulation, long test to distinguish between primary and secondary hypocortisolism)

289
Q

What are the HPA function tests for hypercortisolism?

A

• 24 hour urine free cortisol
• resting ACTH levels
• dexamethasone drug challenge (low-dose test to determine if HPA is normal/abnormal, high dose test to determine pituitary/non-pituitary)

290
Q

How does a short ACTH stimulation test work?

A

Compare blood cortisol levels before and after IV tetracosactide (synthetic ACTH):

  1. If serum cortisol has risen by 2x compared to normal, primary adrenal gland functioning is normal
  2. If ACTH stimulation results in lower cortisol expected, hypo cortisol is occurring—> need long ACTH stimulation test
291
Q

How does the long ACTH stimulation test work?

A

This test differentiates between primary and secondary adrenal insufficiency by using a larger dose of tetracosactide, and multiple administrations. Blood level is taken at one, four, eight, and 24 hours:

  1. If primary hypocortisolism/Addison disease, cortisol level is reduced at all time points
  2. Secondary hypocortisolism, the adrenal gland is still responsive to ACTH but has a delayed production of cortisol (normal response overtime)
292
Q

What is a gold standard screening test for changes in cortisol levels?

A

Dexamethasone suppression test:

• cortisol analog, administration should lead to reduction in CRH and ACTH. Cortisol level should also be reduced if the HPA is functional

293
Q

What is the dexamethasone test interpretation of Cushing disease (pituitary tumor)?

A

• high ACTH level
• low-dose dexamethasone suppression test: no change
• high dose test: normal suppression

294
Q

What is the dexamethasone test result interpretation of Cushing syndrome caused by an adrenal tumor?

A

• ACTH is low
• low-dose dexamethasone suppression test: no change
• high dose test not needed

295
Q

What are the dexamethasone test results of Cushing syndrome related to an ectopic ACTH producing tumor?

A

• ATH level is high
• low-dose dexamethasone suppression test: no change
• high dose test: no change

296
Q

What are the reasons for secondary hyperaldosteronism?

A

• decreased renal perfusion (renal artery stenosis, arterial nephrosclerosis)
• arterial hypovolemia and edema (CHF, cirrhosis, nephrotic syndrome)
• pregnancy (estrogen induces increases in plasma rennin)

297
Q

What is Waterhouse Friderichsen syndrome?

A

• An acute adrenal cortical insufficiency due to overwhelming bacterial infection with Neisseria meningitidis (or pseudomonas, pneumococcal, haemophilus, staphylococcus) more common in children
• rapid progressive hypotension and shock
• DIC with widespread Purpura
• massive adrenal hemorrhagic necrosis and adrenal cortical insufficiency

298
Q

Patients with Addison disease have autoimmune adrenalitis, and autoantibodies to what?

A

21-hydroxylase and 17-hydroxylase

299
Q

What is adrenal pheochromocytoma?

A

• composed of chromaffin cells, releases catacholamines. Rare cause of surgically curable hypertension

300
Q

What is a neuroblastoma?

A

• small blue cell tumor, primitive cells with scant cytoplasm and dark nuclei
• mitotic activity and Karyorrhexis, pleomorphism prominent
• Hommer-wright pseudorosettes can be seen

301
Q

What is a ganglioneuroma?

A

• complete maturation of neuroblastoma
• no residual small blue cell component
• ganglion (arrow) and Schwannn cells
• schwannian stroma in a neuroblastoma is associated with a more favorable prognosis

302
Q

What are the most favorable outcomes for neuroblastoma?

A

age and stage
1. younger than 18 months
2. stage 1, 2, and 4S
3. Neuronal differentiation
4. Hyperdiploidy

303
Q

What indicates a high risk neuroblastoma?

A

MYC amplification

304
Q

What is primary osteoporosis?

A

Deterioration of bone mass that is unassociated with other chronic illnesses. Related to aging and decreasing gonadal function.

305
Q

What is secondary osteoporosis?

A

Osteoporosis that results from chronic conditions that contribute significantly to accelerated bone loss. These chronic conditions include endogenous and exogenous thyroxine excess, hyperparathyroidism, malignancies, gastrointestinal diseases, medication, renal failure, and connective tissue diseases.

306
Q

What is the comparison in a T score DEXA scan?

A

Interpretation of bone density in standard deviations when in comparison to a healthy 35-year-old of the same gender (peak bone mass)

307
Q

What is a Z score of a DEXA scan?

A

Bone density scan in comparison to someone of approximately the same age, sex, ethnicity, height, and weight (similar cohort). Commonly used in menopausal and perimenopausal women

308
Q

What are common secondary causes of osteoporosis?

A

• endocrine (thyroid, hyperparathyroidism, DM, low testosterone)
• G.I. (absorption, etc.)
• renal disease
• medication
• nutrition (low calcium, anorexia, vitamin D deficiency, alcoholism)
• malignancy (multiple myeloma)
• collagen/genetic disorders

309
Q

What is included in a basic workup for secondary osteoporosis?

A
  • CMP with calcium and phosphate
  • CBC
  • vitamin D (25-hydroxy vitamin D)
  • TSH
  • PTH
  • 24 hour urine calcium and creatinine
310
Q

What is primary hyperparathyroidism?

A

Excess production of PTH due to enlargement of one or more of the parathyroid glands. Excess PTH causes hypercalcemia

311
Q

What is secondary hyperparathyroidism?

A

Excess production of PTH produced by the body because calcium levels are too low. Renal failure is the most common cause of secondary hyperparathyroidism. Also seen with low vitamin D levels, or calcium absorption in the gut

312
Q

What are the indications for surgery of a patient patient with hyperparathyroidism?

A

• calcium levels > 1 unit above normal
• osteoporosis
• CrCl (creatinine clearance) < 60
• 24 hour urine calcium > 250 mg/day in women or >300 mg/day in men
• nephrolithiasis or nephrocalcinosis
• age < 50

313
Q

What are the common complications of parathyroid surgery?

A

• increased risk of fracture
• increased urinary tract infections due to kidney stones/blockage
• PUD
• pancreatitis
• pseudogout
• low blood calcium levels—> tetany (peripheral/mouth tingling and muscle twitching)

314
Q

Biguanides: metformin

A

• insulin sensitizer: enhances the effects of insulin by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity
• MECH: suppression of mitochondrial respiratory chain, activation of AMPK, increase insulin receptor TK activity, stimulation of GLUT4 transporter
• SE: lactic acidosis, Caution in renal insufficiency patients, diarrhea

315
Q

Thiazolidinediones: pioglitazone, rosisglitazone

A

• insulin sensitizers: enhance the effects of insulin by increasing uptake and storage of glucose and skeletal muscle/adipose tissue
• MECH: PPAR-gamma ligands that can modulate expression of genes involved in in lipid/glucose metabolism—> increase GLUT1, GLUT4, decreased FFA levels, decreased hepatic glucose output
• SE: weight gain, LE edema, heart failure/CV events, bladder cancer

requires insulin presence for action

316
Q

Sulfonylureas: glimepiride, glipizide, glyburide

A

• insulin secretogogues: promote pancreatic beta cell insulin secretion by binding to sulfonylurea receptor (SUR1) of beta cells (ATP sensitive potassium channel) causing an increased depolarization and release of insulin
• SE: hypoglycemia and weight gain

317
Q

Meglitinides: repaglinide, nateglinide

A

• insulin secretogogues: promote pancreatic beta cell insulin secretion by binding to sulfonylurea receptor (SUR1) of beta cells (ATP sensitive potassium channel) causing an increased depolarization and release of insulin in a different binding site than that of sulfonylurea drugs
• SE: hypoglycemia and weight gain

318
Q

GLP1 agonists: exenatide, semaglutide

A

• Incretin modulators: promote pancreatic beta cell insulin aggregation by stimulating insulin and inhibiting glucagon secretion, delaying gastric emptying, and inducing safety
• SE: pancreatitis, C-cell tumors in individuals with thyroid cancer/MEN2

319
Q

Dipeptidyl peptidase 4 inhibitors (DDP4): sitagliptin (gliptins)

A

• Incretin modulators: promote pancreatic beta cell insulin aggregation by inhibiting the breakdown of incretins (GIP, GLP1)
• SE: GI, pancreatitis

320
Q

Acarbose and miglitol

A

• Alpha-glucosidase inhibitor: impair GI carbohydrate absorption by competitively inhibiting the intestinal alpha-glucosidase enzymes, delaying digestion and absorption of polysaccharides and diet
• SE: GI

321
Q

Pramlintide

A

• Amylinomimetics: slows gastric emptying, promotes satiety by binding to amylin receptors leading to the inhibition of glucagon release and inhibition of glucose synthesis in the liver
• SE: severe hypoglycemia in combination with insulin

322
Q

Canagliflozin and empagliflozon

A

• Sodium glucose transporter-2 (SGLT2) inhibitors: increase glucose excretion by the kidneys in the proximal tubule
• SE: genital infections/urinary tract infections (due to increased glucose excretion) dehydration, polyuria

may have some renal benefits, decreased risk of dialysis, transplantation, death

323
Q

What are the rapid acting insulin preparations?

A

• analogues: insulin lispro, aspart, and glulisine
• inhaled human regular insulin
• typically given as a bolus during meal time to compensate for carbohydrates

324
Q

What is the short acting insulin preparation?

A

• human regular insulin
• typically given as a bolus during meal time for carbohydrate compensation

325
Q

What is the intermediate acting insulin preparation?

A

• human NPH insulin
• given as a basal/background insulin modulator in diabetic patients

326
Q

What are the long acting analog insulin preparations?

A

• insulin glargine, detemir, and degludec
• have a flat peak of action and a long effective duration used for basal/background insulin modulation and diabetic patients

327
Q

What are the common side effects of insulin preparations?

A

• hypoglycemia
• weight gain
• allergic reactions (injection site)
• atrophy or hypertrophy of subcutaneous fat at injection site
• insulin resistance

328
Q

What is maturity onset diabetes of the young (MODY)?

A

• rare, autosomal dominant, monogenetic disorders caused by mutations in single genes that disrupt pancreatic beta cell function

329
Q

What is the pathophysiology of type one diabetes?

A

• insulin is not made because pancreatic beta cells are destroyed
• auto immune process, T cell receptors recognizing self antigen are not eliminated because of genetic defect in immune system —> T cells expressing TCR which recognize beta cell peptides as antigen destroy beta cells

330
Q

What are the immunological characteristics of a patient with type one diabetes?

A

• auto antibodies to islet proteins in patients
• insulitis: infiltration of T cells
• recognize and proliferate in response to beta cell antigens

331
Q

What are the specific MHCII Loci most strongly associated with type 1 diabetes?

A

• DR4-DQ8
• DR3-DQ2

332
Q

What is Teplizumab?

A

Anti-CD3 antibody, blocks TSS interaction with antigen presenting cell. It can delay the progression to clinical type one diabetes

333
Q

What is the cause of type two diabetes?

A

Excess nutrients at cellular level leading to hyperglycemia, increased circulating free fatty acids —> inflammation, regulated lipid metabolism —> insulin resistance —> beta cell destruction, insufficiency (or compensation)

334
Q

What are the genetic risks of developing type two diabetes?

A

• TCF7L2 and PPAR-gamma — transcription factors
• KCNQ1 — potassium ion channel
• zinc transporter
• insulin receptor substrate (IRS)

335
Q

Why does chronic excess nutrition lead to type two diabetes?

A
  1. Adipocytes expand beyond limits of O2 diffusion
  2. Extreme stress —> secretion of MCP-1 —> recruitment of macrophages —> secretion of TNF alpha —> insulin resistance
336
Q

How does TNF alpha secretion lead to insulin resistance?

A

• inhibition of PPAR-gamma
• activation of JNK leading to the inhibition of insulin receptor signaling
• amplification of inflammatory response (activation of NFKB)

337
Q

Elevated levels of free fatty acids lead to what?

A

Insulin resistance and skeletal muscle

338
Q

How is insulin receptor signaling impaired in diabetes type 2?

A

JNK, and AKT are inhibited—> GLUT4 does not move to cell surface in response to insulin

339
Q

What is dysregulated in the liver in type two diabetes?

A
  • ability of insulin to regulate metabolic pathways
  • gluconeogenesis increased (FOXO1)
  • glycogen synthesis decreased (GSK3, glycogen synthesis)
340
Q

What causes pancreatic beta cell destruction in type two diabetes?

A

Insulin resistance amplifying hypernutrition —> oxidative stress, endoplasmic reticulum stress —> apoptosis (unfolded protein response, caspase 1, cytokine IL1-beta)

341
Q

What are the common mechanisms activated by hyperglycemia in type one and type two diabetes?

A
  1. Oxidative and ER stress
  2. Advanced glycation end products (AGE)
  3. Polyol/sorbitol pathway
342
Q

What is advanced glycation end product (AGE/RAGE)?

A

• non-enzymatic modification of proteins by sugar due to hyperglycemic environments
• accumulates in vessel walls promoting cross-linking and additions of bulky non-functional modifications
• binds RAGE on macrophages and causes ROS/release of inflammatory cytokines

343
Q

What is the mechanism of the polyol pathway in diabetes?

A

Hyperglycemia leads to distorted glucose metabolism—> hexokinase is saturated and glucose can enter polyol pathway (creating sorbitol, and depleting NADPH leading to more oxidative stress and increased osmolality/swelling/tissue damage)

344
Q

What type of diabetes has amyloid deposition within the islets?

A

Type two

345
Q

What are the large and medium sized artery (macrovascular) diseases of diabetes?

A

• accelerated atherosclerosis
• stroke
• myocardial infarction
• lower extremity ischemia and peripheral vascular disease

346
Q

What are the small vessel (microvascular) diseases and diabetes?

A

• diabetic retinopathy
• diabetic nephropathy
• diabetic neuropathy

347
Q

What are the four pathways of diabetes pathology?

A
  1. Formation of advanced glycation end (AGE) products
  2. activation of protein kinase C
  3. Oxidative stress and disturbances in the polyol pathways
  4. Hexosamine pathways and generation of fructose-6-phosphate
348
Q

What is the myocardial infarction histology at different stages?

A
  1. Contraction bands at hours- 1-2 days
  2. Neutrophil and then macrophages at 3-4 days
  3. Granulation tissue at 7-10 days
  4. Scar at weeks-months
349
Q

A kidney with renal artery atherosclerosis looks like what?

A

• chronic arterial glomerulosclerosis and arterionephrosclerosis
• granular surface, small kidney, thinned cortex
• Kimmelstei-Wilson nodules peripherally
• glomerular hyaline arteriosclerosis
• tubular basement membrane thickening

350
Q

What are the diabetic ocular complications?

A

• cataracts: opaque lens
• glaucoma: increased intraocular pressure
• retinal vasculopathy and neovascularization

351
Q

Antibodies to what are typically seen in type one diabetes?

A

Glutamic acid decarboxylase (GAD) -65

352
Q

What is the ominous octet?

A
353
Q

Gestational diabetes: glucose tolerance test

A
  1. One hour test, if glucose > 140 mg/dL three hour test
  2. Three hour test: One glucose check every hour, 2 reads > 190 mg/dL indicates gestational diabetes
354
Q

What percentage of women with gestational diabetes will go on to develop type two?

A

50%

355
Q

What situates a diagnosis of diabetes?

A

• fasting plasma glucose greater than one 26 mg/dL on two separate occasions
• random plasma glucose of 200 mg/dL with symptoms (polyuria, polydipsia, weight loss)
• plasma glucose greater than 190 mg/dL three hours after a 75 g oral glucose load (pregnancy)
• glycosylated hemoglobin (A1C) > 6.4%

356
Q

What is a significant side effect of metformin?

A

Lactic acidosis especially when combined with IV contrast

357
Q

What are the best anti-diabetes medication’s for cardiac patients?

A

• GLP-1 agonist and SGLT2 inhibitors

358
Q

What medication is most likely to reduce A1c?

A

Insulin

359
Q

What are the associated metabolic abnormalities of patients with diabetes?

A

• steatohepatitis
• elevated triglycerides/low HDL
• hyperuricemia (gout)
• acanthosis nigricans

360
Q

Patients with diabetes are more likely to develop what?

A

• heart disease and stroke (2-4x)
• kidney failure (44% of new cases)
• blindness (leading cause)
• lower limb amputations (over 60% of new cases)

361
Q

What is the fluid deficit of a patient in DKA?

A

Typically 100 mL/Kg — fluid replacement is essential

362
Q

What are the cluster symptoms of a patient with metabolic syndrome?

A

• hypertension > 130/80
• hypertriglyceridemia > 150
• low HDL cholesterol < 40 in men, < 50 in women
• obesity (central-apple shaped) BMI > 30
• impaired glucose handling (insulin resistance) BG > 100
• microalbuminuria

363
Q

Metabolic syndrome can lead to what blood state?

A

• prothrombotic state
• elevated fibrinogen, plasminogen activator inhibitor-1, and other coag factors
• TX: low-dose aspirin, clopidogrel

364
Q

Patients with metabolic syndrome and _________ were twice as likely to die from heart disease or stroke.

A

Sleep deprivation— fewer than six hours per night

365
Q

What is the most important source of blood glucose?

A

The liver via glycogenolysis and gluconeogenesis

366
Q

What does increased blood glucose (and therefore insulin) stimulate in the body?

A

• increased glycogen synthesis
• increased fatty acid synthesis
• increased triglyceride synthesis
• increased liver glycolysis

367
Q

What does decreased glucose (and therefore glucagon release) stimulate in the body?

A

• increased glycogenolysis
• increased gluconeogenesis
• increased lipolysis
• decreased liver glycolysis

368
Q

What is MODY2 (maturity onset diabetes of the young type two)?

A

• autosomal dominant call by mutation and Glucokinase
• insulin is not released appropriately when blood glucose increases

369
Q

What are the key enzymes of gluconeogenesis?

A

• glucose 6-phosphatase
• PEP-CK

~ their expression is controlled by transcription factor FOX01

370
Q

What blocks the transcription factor FOX01?

A

PKB (Akt), which is activated by insulin

371
Q

What enzymes are required for hepatic gluconeogenesis?

A
  • CREB
  • PGC1-alpha

~ glucagon stimulates protein kinase A (PKA) through cAMP —> PKA phosphorylates CREB —> CRE activates PGC1-alpha

372
Q

What inhibits growth hormone release?

A

• Somatostatin
• IGF-1 (insulin-like growth factor) by inhibiting GHRH

373
Q

What type of receptor is the growth hormone receptor?

A

JAK/STAT

374
Q

In the liver, thyroid hormone receptor activation increases transcriptions of genes that:

A

promote gluconeogenesis, fatty acid biosynthesis, and bile acid synthesis

375
Q

Where are the germ cell follicles located in the ovary?

A

In the cortex

376
Q

Oogenesis: third fetal month

A

• oogonia enlarge and become primary oocyte
• divide up until prophase of meiosis 1 (arrested here until adulthood)

377
Q

Oogenesis: adult

A
  • first meiotic division completed just prior to ovulation (one oocyte per month)
  • secondary oocyte proceeds to metaphase 2 of meiosis 2 (arrested here until fertilization)
378
Q

Oogenesis visual: image/chart

A
379
Q

What is contained within a primordial follicle in the ovary?

A
  • primary oocyte (arrested in prophase of meiosis 1)
  • follicular cells (single layer of flattened cells, germinal epithelial cells)
  • FSH receptors: responsive to maturation stimulus
380
Q

Image/graph depicting the entire menstrual cycle: tissue, oocyte development, hormones

A
381
Q

Describe a primary follicle of the ovary

A

• primary oocyte
• follicular cells divide, become columnar and stratified (granulosa cells) —> these contribute to the zona pellucida (eosinophilic gel like neutral protein)

382
Q

Secondary follicle of the ovary

A

• primary oocyte still in prophase 1
• follicular fluid production (granulosa cells secrete GAGs/proteoglycans that generate osmotic gradient to draw water into the theca interna)
• Antrum (fluid filled a space) begins to form

383
Q

Describe the Theca interna of the secondary follicle of the ovary

A

• highly vascular
• epithelioid
• smooth ER, produces androgens

384
Q

What do the granulosa cells of secondary ovarian follicles do?

A

• produce aromatase to convert hydrogen into estrogen
• response to FSH by secreting inhibin (negative feedback)
• estrogen increases FSH receptors

385
Q

What are the layers of a mature (Graafian) follicle of the ovary?

A
  • corona radiata: granulosa cells in direct contact with the oocyte, cells radially arranged around zona pellucida
  • cumulus oophorus: granulosa cells that anchor the oocyte to the basal lamina
  • theca folliculi: reach their greatest development and produces androgens
386
Q

What signals for final maturation, pushing the oocyte into metaphase of meiosis 2?

A

Luteinizing hormone

387
Q

What is stigma formation during ovulation?

A

• thinning of ovarian wall adjacent to tunica albuginea
• decreased blood flow, protease released by follicle cells
• rupture of epithelium and explosion of cumulus mass and follicular fluid—> captured by oviductal fimbriae

388
Q

What does follicle stimulating hormone (FSH) do in ovulation?

A

• stimulates granulosa cell growth and estrogen synthesis
• stimulates the formation of LH receptors and augments responsiveness

389
Q

What does luteinizing hormone (LH) due in folliculigenesis?

A

• stimulates thecal cell growth and androgen production
• stimulates progesterone production in granulosa cells

390
Q

What is the corpus luteum?

A

• temporary glandular structure derived from remnants of ruptured follicle following ovulation
• granulosa sells become granulosa lutein cells
• theca interna cells become theca lutein cells

391
Q

What is the corpus luteum of pregnancy?

A

• corpus luteum graviditatis
• forms shortly after implantation (around nine days)
• becomes large, around 5 cm
• maintained by hCG produced by trophoblast of placenta and persists during first trimester

392
Q

What is estrogen?

A

• produced primarily by growing follicles (theca makes androgen, granulosa converts to estrogen via aromatase)
• induces maturation of female reproductive tract and mammary glands
• directs the repair of the uterus following menstruation and influences growth of mammary glands in pregnancy

393
Q

What is progesterone?

A

• produced primarily by corpus luteum (post ovulatory levels are high)
• causes uterine gland to secrete and prepares uterus for implantation of fertilized ovum
• aids in the growth of mammary glands
• inhibits uterine contractions (allowing for pregnancy)

394
Q

What is Relaxin?

A

• produced by corpus luteum and decidual cells of the placenta
• inhibits contractions of myometrium during pregnancy and promotes dilation of the cervix by softening it

395
Q

What is Inhibin?

A

• produced by granulosa cells, found in follicular fluid
• negative feedback to anterior pituitary, reduces FSH release

396
Q

What is an atretic follicle?

A

• follicular atresia, oocyte degenerates first, then follicular cells and then theca interna (inside out)
• entire structure replaced by scar tissue and can occur at any stage of oogenesis

397
Q

What are the four anatomical divisions of the oviduct?

A

1. Infundibulum: funnel shaped opening near the ovary with its fimbriae
2. Ampulla: sight of fertilization
3. Isthmus: narrowing
4. Intermural portion: lies within uterine wall and opens into cavity of uterus

398
Q

What are the three layers of the oviduct?

A
  1. Mucosa (endosalpinx— simple columnar)
  2. Muscularis (myosalpinx)
  3. Serosa (peritoneal/mesothelial cells— simple squamous)
399
Q

What cells make up the infundibulum and the ampulla of the oviduct?

A

• simple columnar epithelium with ciliated cells stimulated by estrogen (transport)
• secretory cells: non-ciliated, peg cells (fluid production, proteins, ions, stimulated by progesterone)

400
Q

Image of the different sections (intermural, isthmus, ampulla) of the oviduct

A
401
Q

What are the layers of the uterus?

A
  1. Endometrium (mucosa)
  2. Myometrium (muscularis)
  3. Perimetrium (serosa)
402
Q

Layers of the endometrium:

A

• epithelium: simple tubular glands (exocrine) and a simple columnar epithelium, and lamina propria
• basal layer: deepest, not shed during menstruation (responsible for regeneration of the functional layer)
• functional layer: superficial and deep layers, responsible for shedding during menstruation

403
Q

What are the two layers of the functional layer of the endometrium of the uterus?

A
  1. Superficial compact layer:
    • narrow, ciliated cell
    • no edema
    • contains a straight portions of tubular glands
  2. Deep spongy layer
    • thick, secretory cells
    • edematous
    • glance or tortuous and have large lumens
404
Q

Myometrium: when are the muscle fibers shortest versus longest?

A

• shortest: the week after menstruation
• longest: fourth week of the cycle

~ cyclical every 28 days, hormone responsive

405
Q

Blood supply of uterus:

A
406
Q

What are the phases of the menstrual cycle?

A
  1. Proliferative phase (estrogenic, follicular)
  2. Secretory phase (progestational, luteal)
  3. Premenstrual (ischemic)
  4. Repair phase
407
Q

Proliferative phase of the menstrual cycle:

A

• days 7-14
• begins at end of menstrual flow and repair
• induced by estrogen, 2-3x increase in endometrial thickness
• straight tubular glands increase in number and length, cells accumulate glycogen
• coiled arteries elongate

408
Q

Secretory phase of the menstrual cycle:

A

• days 15-26
• ovulation precipitates formation of corpus luteum
• progression increases dramatically, estrogen increases slightly
• endometrial thickening continues (strum edema, gland dilate and become secular/tortuous)
• glycogen salts and protein increase

409
Q

Premenstrual (ischemic) phase of the menstrual cycle

A

• days 26-28
• corpus luteum regresses, decreases steroid output (decreased progesterone)
• coiled arteries constrict intermittently leading to ischemia and necrosis
• leukocyte infiltration occurs

410
Q

Menstrual and repair phases of the menstrual cycle:

A

• menstrual: days 1-4
• functional layer of endometrium undergo complete necrosis and his shed

• repair phase: days 5-6
• Denuded surface is re-epithelialized and coiled arteries regrowth

411
Q

What is the difference between estrogenic and gestrogenic mucus of the cervix?

A

• estrogenic: at ovulation, low viscosity, permits sperm migration, egg white consistency

• gestrogenic: high viscosity, prevents fertilization of the wrong time by inhibiting particle passage

412
Q

What is the abrupt epithelial change in the cervix at the external cervical os?

A

Simple columnar with occasional ciliation —> Stratified squamous non-keratinized epithelium

~ squamocolumnar junction is site of most pre-cancerous lesions

413
Q

What happens to the vagina during high levels of estrogen?

A

• estrogen stimulates epithelial cells to synthesize and store glycogen, which is metabolized by lactobacilli
• produces lactic acid and an acidic environment (low pH in vaginal lumen helps restrict pathogenic invasion)

414
Q

What is kisspeptin?

A

• neuropeptide, ligand of G protein coupled receptor 54
• mutation can cause hypogonadotrophic hypogonadism
• pulsatile kisspeptin increase occurs at puberty onset

415
Q

Luteinizing hormone (LH) levels above what is suggestive of central activation of puberty?

A

0.3-0.55 IU/L

416
Q

What is adrenarche?

A

• onset of adrenal androgen production, independent of the pubertal maturation of the HPG axis
• secretes weak hydrogens DHEA and DHEAS, and androstenedione Beginning at age 6/7 in girls and 7/8 in boys

417
Q

What is pubarche?

A

Onset of sexual hair growth (androgen effect)

418
Q

What is Thelarche?

A

Onset of breast development (estrogen effect)

419
Q

What is menarche?

A

Onset of menses

420
Q

What is gonadarche?

A

The onset of pubertal function of the gonads (sex hormone production, gametogenesis)

421
Q

What is spermarche?

A

The appearance of spermatozoa in Seminal fluid

422
Q

Tanner stages of development:

A

Tanner stage two classified by breast development in women, and testicular size in menis considered puberty onset

423
Q

What influences the age of onset of puberty?

A

• genetics
• nutritional status (higher BMI= earlier puberty onset. Malnutrition/illness= delayed puberty)
• skeletal maturation (puberty stage correlates better with bone age than chronological age)
• stress, trauma, ACEs

424
Q

What are the adverse health impacts associated with early puberty?

A

• reduced adult height
• cancer: testicular/breast
• metabolic syndrome
• polycystic ovarian syndrome
• risky behavior and substance use
• depression and eating disorders

425
Q

What is precocious puberty?

A

Girls: onset of breast development before age 8

Boys: increase testicular volume (>4mL) boys before age 9

~ progressive and accompanied by acceleration of bone age and linear growth

426
Q

What is the definition of delayed puberty?

A

The absence of somatic signs of puberty development at an age to standard deviations higher than the mean (approximately 14 for boys and 13 for girls)

427
Q

What is true puberty?

A

Onset of Tanner stage 2:

Girls: presence of visible breast buds
Boys: testicular volume > 4mL or length of the ovoid testicle >2.5cm

428
Q

What is Gonadotropin-dependent precocious puberty?

A

• central precocious puberty involving HPG axis
• true puberty, puberty levels of gonadotropins
• producing sex steroids
• normal puberty sequence of events happening earlier
• isosexual (development aligned with biological sex)

429
Q

What is Gonadotropin-independent precocious puberty?

A

• peripheral precocious puberty
• pseudoprecocious puberty
• pre-puberty levels of gonadotropins, sex steroids may be from gonads or non-gonadal sources (adrenal, exogenous, ectopic)
• abnormal sequence of events
• can be isosexual or contrasexual

430
Q

What are some causes of gonadotropin-dependent central precocious puberty?

A

• CNS lesions: hypothalamic hamartoma, tumors, cerebral malformation, CNS injury
• idiopathic (most common)
• genetic
• internal adoption

431
Q

What are some causes of gonadotropin-independent peripheral precocious puberty?

A

• autonomous gonadal activation: McCune Albright syndrome, genetic disorder
• tumors: gonads, liver, mediastinum
• adrenal: congenital adrenal hyperplasia
• exogenous sex steroids

432
Q

What is premature thelarche?

A

• transient breast development between 6 to 12 months of age
• spontaneously regressed by three years, no other secondary sex characteristic development
• no height acceleration

433
Q

What is premature adrenarche?

A

• pubic and/or axillary hair before 8 years
• no other secondary sex characteristic development
• no height acceleration

434
Q

What is the evaluation for a patient with precocious puberty?

A
435
Q

What are some primary causes of delayed puberty (hypergonadotropic hypogonadism)

A

• genetic:
- Kleinfelter syndrome (47, XXY)
- Turner syndrome (45, XO)
- Female carriers of fragile X

• acquired:
- Chemotherapy, radiation
- Infectious disease (mumps)
- Autoimmune (oophiritis)
- Gonadal trauma/surgery

436
Q

What are some secondary/tertiary causes of delayed puberty (hypogonadotropic hypogonadism)

A

• pathologic: abnormal HPG
- Congenital GnRH deficiency
- Acquired: trauma, tumor, infiltrative disease

• physiologic: functional issue with HPG
- secondary chronic illness: leukemia, anorexia
- functional hypothalamic amenorrhea

HRM (3 decks)

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