Principles of Endocrinology Flashcards

1
Q

The pituitary gland receives inputs from . . .

A
  1. The brain (via the hypothalamus)
  2. The blood stream (via mediators released from other endocrine glands and metabolically active sites)
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2
Q

Why is the pituitary gland also called the “master gland?”

A

Because it releases hormones that control the activity of many other glands in the body. Think TSH for the thyroid, ACTH for the adrenal gland, leutenizing hormone for reproductive glands, etc.

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3
Q

Location of the pituitary gland

A

Located centrally in the cranium in a small fossa (depression) called the sella turcica (aka Turkish saddle).

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4
Q

Sellar diaphragm

A

Infold of the dura mater which separates the pituitary gland from the main cranial cavity and protects it. A “pituitary stalk” goes through the sellar diaphragm connecting the pituitary gland to the hypothalamus.

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5
Q

Location of pituitary within skull floor

A
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6
Q

Important structures adjacent to the pituitary gland

A
  • Optic chiasm (superoanterior to the gland)
  • Cavernous sinuses, laterally, containing:
    • CN IV, V, and VI (ocular movements)
    • CN V1 and V2 (trigeminal, facial sensation)
    • Cavernous segment of the internal carotid artery
  • Sphenoid sinus inferior to the gland, just above the nasopharynx
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7
Q

Most pituitary surgeries are now done via. . .

A

. . . the sphenoid sinus by way of the nasopharynx using long tools, and are accompanied by dopplar ultrasound to avoid the internal carotid artery.

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8
Q

Nettergram demonstrating anatomical relationships of the pituitary gland and other important structures

A
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9
Q

Radiologic examination of the pituitary

A

Pituitary MRI

This involves use of gadolinium contrast.

The pituitary is surrounded by bony structures, making X-ray difficult. CT is also an option, but has poor resolution for the pituitary.

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10
Q

Standard pituitary radiology. What are the structures?

A

A - optic chiasm

B - Hypothalamus

C - Pituitary stalk

D - Posterior pituitary (shows a characteristic “bright spot” due to presence of ADH vesicles)

E - Anterior pituitary

F - Suprasellar cistern

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11
Q

Pituitary embryology

A

The anterior and posterior have separate origins!

The anterior is derived from the surface ectoderm, and forms form an upward outpouch of primitive oral cavity tissue called Rathke’s pouch. Meanwhile, the posterior is derived from the neuroectoderm, and forms from a downward outpouch of brain called the infundibulum via an intermediate structure called the pars nervosa.

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12
Q

Rathke’s pouch cyst

A

In adulthood, a small slit (Rathke’s cleft) can sometimes be seen in the pituitary which is the remnant of the fetal pouch – in some cases, this slit can fill with fluid and exert local mass effects with deleterious effects.

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13
Q

Hypothalamo-hypophyseal portal system

A

Portal venous system supplying the anterior pituitary gland. Blood in this system comes from the internal carotid artery, but passes first through the hypothalamic capillaries. The resulting milieu is low-pressure and rich in hypothalamic signaling molecules.

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14
Q

GnRH neurons

A

These neurons originate at the olfactory placode, where the neurons responsible for the sense of smell also originate. They migrate to the hypothalamus under the control of a range of transcription factors. A failure to migrate can lead to absent GnRH and therefore absent sexual development, a condition called idiopathic hypogonadotropic hypogonadism.

If the sense of smell is also absent, it is called Kallman syndrome.

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15
Q

Production and storage of posterior pituitary hormones

A
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16
Q

Hormone-producing cells of the anterior pituitary gland

A
  • Somatotropes : GH-secreting
  • Lactotropes : Prolactin-secreting
  • Corticotropes : ACTH-secreting
  • Gonadotropes : FSH and LH-secreting
  • Thyrotropes : TSH-secreting
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17
Q

The posterior pituitary gland consists of. . .

A

. . . axons and glial cells

The nerve cell bodies for these axons are located in the hypothalamus, primarily in the paraventricular nucleus (responsible for oxytocin) and supraoptic nucleus (responsible for ADH)

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18
Q

Pars Nervosa histology

A

c - capillaries

p - pituicytes, a type of glial cell, most numerous cell present

NB - neurosecretory bodies from which oxytocin or vasopressin is released upon stimulation

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19
Q

ADH / Vasopressin

A

Reduces urinary volume by increasing water permeability of the renal collecting ducts

Stimulus: Increased plasma osmolality, decreased plasma volume

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20
Q

Oxytocin

A

Stimulates contraction of mammary gland myoepithelial cells (important in lactation) and uterine smooth muscle

Stimulis: Suckling / nipple stimulation, Baby’s cry, Mechanical stimulation of cervix

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21
Q

Regulation of ADH

A

The overall purpose of this hormone is to promote water retention.

If the person drinks a lot of water, the hormone level is low, allowing most of the water to be quickly excreted by the kidney.

If the person drinks very little water, the hormone level is high to ensure that the water is being retained in the body and not excreted.

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22
Q

Mechanism of ADH regulation and action

A
  • Inputs:
    • Pressure sensors (aortic arch, cardiac atria, carotid sinus)
    • Osmolality sensors
    • Osmolality response more sensitive than pressure response
  • ADH acts on V1 receptors in smooth muscle, promoting contraction and increased SVR
  • ADH acts on V2 receptors in collecting duct of kidney to increase permeability (insertion of vesicle-sequestered AQP2)
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23
Q

Diabetes insipidus

A

Deficiency of ADH resulting in the production of large quantities of dilute urine

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24
Q

Hormones secreted by anterior pituitary

A
  • Growth hormone
  • FSH
  • LH
  • ACTH
  • TSH
  • Prolactin
  • MSH
  • Endorphins
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25
Q

Classes of anterior pituitary hormones

A
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26
Q

Summary of anterior pituitary function

A
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27
Q

The hypothalamus and pituitary are located outside. . .

A

. . . the blood-brain barrier

And this is key to their function.

28
Q

How do mediators released into the hypothalamic-hypophyseal portal system interact with the anterior pituitary gland?

A

G-protein coupled receptor signaling

29
Q

Hypothalamic peptides in general circulation

A

Broken down and/or too low concentration to be detectable after being diluted by entry into the systemic venous system

30
Q

Secretion of the hypothalamic releasing hormones occurs in . . .

A

. . . repetitive bursts rather than a constant, steady stream, interspersed with large breaks in secretory activity

31
Q
A
32
Q

Things that regulate the level of hypothalamic pulsatile secretions

A
  • Clock of the suprachiasmatic nucleus
  • Circadian clocks
  • Sleep cycle
  • Physiologic and/or pathophysiologic adaptation
33
Q

Tropic hormones

A

Hormones that regulate synthesis and secretion of other hormones

34
Q

Pituitary feedback regulation

A
35
Q

Example of a positive pituitary feedback regulation loop

A

LSH/FSH spike just prior to ovulation

36
Q

Growth hormone actions

A
  • Acts directly on certain tissues to alter nutrient metabolism. Can lead to hyperglycemia, as well as other metabolic effects on carbohydrate, lipid and protein metabolism (promotes nitrogen retention).
  • Acts indirectly by stimulating secretion of insulin-like growth factor-1 (IGF-1) production in the liver, which a) acts to promote tissue growth, b) is very imporant for proper bone elongation, and c) stimulates muscle synthesis.
37
Q

IGFBP-3

A

IGF-binding-protein-3

Production stimulated in the liver by Growth Hormone. This protein binds IGF-1 and slows its degradation, and limits the amount of free, unbound, IGF-1 available to exert the effects of the hormone.

38
Q

Regulators of GH levels

A
  • Growth-hormone-releasing-hormone (GNRH) (+)
  • Somatostatin (-)
  • Ghrelin (+)
  • Slow-wave sleep (+)
  • Hypoglycemia (-)
39
Q

Growth hormone excess

A
  • Almost always caused by a pituitary adenoma of stomatotropic cells.
  • Rare, with no biological sex preference, peak incidence in 30’s
  • If developed during childhood, results in gigantism. Linear growth can occur because the epiphyseal growth plates are still open.
  • If developed after epiphyseal growth plates close, results in acromegaly, with growth of the bones of the hands, feet and face.
40
Q

Acromegaly comorbidities

A
  • Enlargement of tongue makes sleep apnea prevalent
  • Effects on organs may lead to cardiomegaly, hypertrophic cardiomyopathy, colonic polyps / colon cancer, multinodular goiter, and other effects
  • Due to common etiology of pituitary adenocarcinoma, other pituitary hormone production is often impeded. Sexual issues are common
  • Anatomic relationships make visual field obstruction and headaches common
  • Fatigue, fluid retention (with carpal tunnel syndrome), joint problems (arthropathy), hyperglycemia, hypertension, sweating and skin tags.
41
Q

Diagnosing acromegaly

A
  • Diagnosis often delayed due to chronic course of changes. Old photographs for comparison are often helpful.
  • An IGF-1 level is a good screening test – it is high in most patients with growth hormone excess
  • The gold standard diagnostic test is the growth hormone level after a 75 gram oral glucose tolerance test – the glucose load should suppress the growth hormone levels and failure to do so is diagnostic of GH excess
42
Q

Treating acromegaly

A

The goal of treatment is to bring IGF-1 levels to normal and for GH levels to suppress to <1 during an oral glucose tolerance test.

Most patients undergo surgical resection of adenocarcinoma. However, this is not always curative.

Somatostatin analogs (octreotide and lanreotide) may be used to suppress GH and IGF-1 levels.

Pegvisomant (Growth hormone receptor antagonist)

Dopamine agonists, like bromocriptine and cabergoline (Dopamine also stimulates normal somatotropes to release GH. However, the abnormal somatotropes in a patient with acromegaly can respond to dopamine with a paradoxical decrease in growth hormone secretion.)

Radiation therapy is sometimes used but is generally not preferred.

43
Q

ACTH

A

Acts on the adrenal glands, stimulating growth and function of adrenal cortex, including adrenocortical steroids: cortisol, aldosterone, and adrenal androgens.

Produced by corticotropes.

Derived from a larger precursor polypeptide called proopiomelanocortin (POMC) that is cleaved by proteolysis to yield several biologically relevant peptide fragments

44
Q

Proopiomelanocortin processing

A

The only three we are responsible for are ACTH, MSH (melanocyte-stimulating hormone), and endorphins.

45
Q

α-MSH

A

α-MSH (and some other hormones that act on the melanocortin receptor) stimulate melanin production in melanocytes, and can lead to a darker skin hue

46
Q

ACTH regulation

A
  • Hypothalamic: Corticotropin-releasing hormone (CRH) (+)
  • Posterior pituitary: Vasopressin (mild +)
  • Physiologic: stress, hypoglycemia, illness, surgery, trauma and infection, circadian rhythm
  • Adrenal: Cortisol and other glucocorticoids (-)
47
Q

Hypothalamic-adrenal-pituitary axis

A
48
Q

Growth hormone axis

A
49
Q

Long endocrine feedback vs short endocrine feedback vs ultra-short endocrine feedback

A

“Long” feedback describes the target organ hormone inhibiting the hypothalamic and pituitary secretion

“Short” feedback describes the anterior pituitary hormone inhibiting the hypothalamic stimulating hormone secretion

“Ultra-short” feedback describes the hypothalamic hormone inhibiting its own secretion at the hypothalamus

50
Q

A ___ TSH level is susipcious for hypothyroidism.

A ___ TSH level is suspicious for hyperthyroidism.

A

A high TSH level is susipcious for hypothyroidism.

A low TSH level is suspicious for hyperthyroidism.

51
Q

A hormone level may not be interpreted in ____,

A

A hormone level may not be interpreted in isolation.

52
Q

Interpretation of controlled and parameter hormone levels

A
53
Q

Stimulation test

A

Administer recombinant or mimetic tropic hormone to elicit hormone release. Done to test deficiency in hormone release.

54
Q

Suppression test

A

Administer a mimetic, but distinct, terminal hormone and wait a predetermined period of time. Then measure the target hormone level.

This is a test of tropic hormone release and function. Levels are expected to go down, but if they do not, there is problem with overproduction at the level of either the tropic hormone or the target hormone.

55
Q

More detailed GH axis (with multiple inputs)

A
56
Q

Glucose tolerance test

A

Administer glucose and then monitor GH or IGF-1 levels.

Levels should go down. If not, there is pathological excessive growth hormone production.

57
Q

Arginine or L-dopa tolerance test

A

Administer arginine and/or L-dopa, then measure GH or IGF-1 levels. Should go up. Otherwise, there is a pathological lack of proper GH production.

58
Q

Diurnal rhythm

A

A diurnal rhythm is a biological rhythm that is synchronized with the day/night cycle

59
Q

Thyroid hormone receptor classes

A
60
Q

In cases where effector endocrine hormone is high but tropic hormone is within the normal range, ___ is probably the problem.

A

In cases where effector endocrine hormone is high but tropic hormone is within the normal range, the pituitary is probably the problem.

It is not being inhibited in the way that it should.

61
Q

Dexamethosone challenge test

A

Suppression test for ACTH function. Cortisol should go down due to decreased ACTH activity. If it fails to go down after a certain period of time, then either the pituitary or endocrine gland is overproducing. This would indicate a diagnosis of Cushing syndrome.

62
Q

Role of urine and saliva analysis in endocrinology

A

Can be used to testimate the “area under the curve” for endocrine hormones. Saliva is used for cortisol, urine is used for many other hormones.

63
Q

Non-morphologic symptoms of GH excess

A
  • Frequent sweating
  • Skin tags
  • Arthritis
  • Carpal tunnel syndrome
64
Q

One good way to survey for acromegaly is to ask an adult patient if they have ___ lately.

A

One good way to survey for acromegaly is to ask an adult patient if they have needed to buy larger shoes lately.

65
Q

___ is responsible for the closure of the epiphyseal plates

A

Androgen signaling is responsible for the closure of the epiphyseal plates.

This is why they tend to close during puberty. Consequently, interference with the androgen signaling pathway leads to persistence of these plates. This would be under the control of FSH and LH, tropic hormones which regulate the level of estrogen and testosterone.

66
Q

Acromegaly treatments and their effects on GH and IGF-1

A