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M2 Endo/Repro > 2/10 Hypothal Pit Disorders - Meininger > Flashcards

2/10 Hypothal Pit Disorders - Meininger Flashcards

1
Q

ANATOMY

hypothal and pituitary

A

both sit at base of brain

pituitary aka “master gland” → control many other endocrine organs (thyroid, adrenals, testes/ovaries)

  • sits in sella turcica (‘Turkish saddle’) → surrounded by bone on all sides except superiorly
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2
Q

pituitary parts

A
  1. pars nervosa (post pit)
    • connected to hypothal via pituitary stalk → post pit is a storage area for hypothal hormones
  2. pars intermedia
  3. pars tuberalis
  4. pars distalis (ant pit)
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3
Q

pituitary adenomas

A

most common to least common

  1. prolactinoma
    • PRIMARY TX: medical tx with dopamine agonist! (decreases prolactin and shrinks tumor)
  2. gonadotroph/non-secr adenoma
  3. GH-secreting adenoma → acromegaly
  4. ACTH-secreting adenoma → Cushing’s disease
  5. TSH-secreting adenoma

2-5: primary tx is SURGERY, radiation, then med tx

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4
Q

consequences of pituitary tumors

A
  • hypopituitarism → not enough space for actual fxal cells to grow into and operate in
  • optic nerve/chiasm compression → visual field abnormalities
  • pituitary stalk compression → central DI
  • CSF leak / meningitis
  • cavernous sinus invasion → CN palsy
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5
Q

visual field issues

  • optic nerve compression
  • optic chiasm compression
  • optic tract compression
A

optic nerve comp

optic chiasm comp: bitemporal hemianopsia

optic tract comp

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6
Q

pituitary fx abnormalities

A

hypersecretion & hyposecretion

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7
Q

hormone terminology

  • “levels”
  • organs
  • produce…
A
  • tertiary/central: hypothalamus → RELEASING HORMONES
    • TRH, GnRH, CRH
  • secondary/central: pituitary → TROPHIC HORMONES
  • primary/end-organ: endocrine organ →
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8
Q

anterior pituitary hormones

A
  1. somatotrophs
    • growth hormone (GH)
  2. gonadotrophs
    • follicle stim hormone (FSH)
    • luteinizing hormone (LH)
  3. corticotrophs
    • adrenocorticotrophic hormone (ACTH)
  4. thyrotrophs
    • thyroid stim hormone (TSH)
  5. lactotrophs
    • prolactin (PRL)
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9
Q

posterior pituitary hormones

A
  1. antidiuretic hormone (ADH) aka vasopressin
    • lesions affecting these neurons → central DI
  2. oxytocin

*both made in hypothalamus, stored and released from post pit

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10
Q

hypersecretion

A

excess hormone secretion from ant pituitary cells

  • GH → gigantism, acromegaly
  • LH/FSH → precocious puberty, central hypergonadism
  • ACTH → Cushing’s disease
  • TSH → central hyperthyroidism

or…

release of tonic dopamine inhibition (PRL)

  • PRL → hyperprolactinemia → decr gonadotropins
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11
Q

hyposecretion

A

result of anatomic lesions affecting anterior pit

  • GH → pit dwarfism, adult GH def
  • LH/FSH → secondary hypogonadism
  • ACTH → secondary adrenal insuff
  • TSH → secondary hypothyroidism
  • PRL → failure to lactate
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12
Q

acromegaly

what is it

signs/sx

normal axis

A

GH excess

  • enlargement at periphery → hands, feet

GH axis: normal

  • interplay of GHRH and somatostatin
    • hypothal releases GHRH → stim GH release
    • hypothal releases somatostain → inhib GH release
  • GH stimulates liver to release IGF1

negative feedback:

  • GH on hypothal and pituitary
  • IGF1 on hypothal and pituitary
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13
Q

endocrine testing principle

hypo and hyper secretion

A

to rule out hyposecretion…

  • stimulate that endocrine axis

to rule out hypersecretion…

  • suppress that endocrine axis (ex. dexamethasone suppression test → neg feedback on pituitary to decr ACTH secretion)
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14
Q

acromegaly

dx/tx

A

dx:

  • elevated IGF1
  • GH NOT suppressed 1hr post oral glucose tolerance test

tx:

  • surgical
  • rad
  • pharma
    • octreotice (somatostain analog)
    • pegvisomant (GH receptor antagonist)
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15
Q

GH deficiency

A

deficiency of something along the axis:

  • GHRH from hypothal
  • GH form pituitary
  • IGF1 from liver

clinical signs/sx

  • children: short stature, frontal bossing, central obesity, high pitched voice
  • adult: decr bone density, abnl lipid profile, dep/decr well being, central obesity

etiology

  • NEUROENDOCRINE
    • congenital/inherited
      • septo-optic dysplasia
    • acquired
      • anatomic lesions (pituitary, hypothal, craniopharyngioma)
      • fx/idiopathic (starvation, child abuse, failure to thrive)
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16
Q

GH deficiency

dx

tx

A

dx

  • stimulation test
    • insulin tolerance test
    • arginine
    • GHRH
    • exercise

tx

  • pharmacological
    • GH
    • GHRH
17
Q

hypothal-pit-gonadal axis

A

GNRH from hypothal is released in PULSATILE fashion

  1. LH from pituitary is released in PULSATILE fashion
    • testosterone production from Leydig cells
    • ovarian steroidogenesis
  2. FSH is non-pulsatile
    • spermatogenesis
    • growth of ovarian follicular granulosa cell
18
Q

abnormalities of HPG axis

4 categories

A
  1. congenital/inherited
    • Kallman’s syndrome (isolated gonadotropin def w anosmia or hypoosmia)
  2. acquired
    • anatomic lesions (hypothal, pit)
  3. functional/idiopathic
    • starvation/low body weight
    • delayed puberty
    • precocious puberty
  4. ectopic
    • ectopic hCG, nonseminoma gernm cell tumors, lung carcinomas, hepatomas
19
Q

HPG axis abnormalities

clinical manifestations

A
  1. hypogonadism
    • amenorrhea
    • gynecomastia
    • infertility
    • decr libido
    • absence or decr in secondary sexual chars
    • osteoporosis
  2. hypergonadism
    • premature secondary sex chars
20
Q

HPG axis abnormalities

tx

A

congenital/inherited

  • Kallman’s syndrome
    • pulsatile GnRH
    • use of hCG and hMGs (FSH)

acquired

  • pit surgery

fxal/idiopathic

  • incr body weight (anorexia nervosa, rigorous exercise)
  • precocious puberty (long acting GnRH agonists)

miscellaneous (might not hit all aspects of disease…ex. fertility)

  • estrogen/progesterone replacement
  • testosterone replacement
21
Q

Cushing’s disease

what axis?

A

HPA

hypothal-pit-adrenal axis

22
Q

hypothalamus-pituitary-adrenal axis

normal

A
  • hypothal releases CRH
  • pituitary releases corticotropin
  • adrenals release cortisol

negative feedback

  • cortisol exercises negative feedback on hypothal and pituitary
23
Q

Cushing’s SYNDROME

(and where Cushing’s disease falls within that)

A

excess cortisol in body

causes can be…

  1. ACTH-dependent
    • Cushing’s disease: incr in pit ACTH
    • ectopic ACTH
  2. ACTH-indep
    • ​​adrenal adenoma or carcinoma
    • iatrogenic (MOST COMMON)
24
Q

clinical manifestations of Cushing’s Disease

A
25
Q

Cushing’s Disease

dx/tx

A

dx

  • 1mg overnight dexamethasone suppression test
  • 24h urine free cortisol

tx

  • surgical
    • pituitary
    • adrenal (rare) → can result in Nelson’s Syndrome
  • radiation
  • pharmacological
    • ketoconazole, metyrapone, aminoglutethimide → inhibit adrenal steroid enzymes
26
Q

secondary adrenocortical insufficiency

causes

A

most common type of adrenal insuff (often iatrogenic)

  1. acquired
    • anatomic lesions (pituitary, hypothal)
  2. pharma
    • withdrawal of prescribed glucocorticoids
    • withdrawal of medications with glucocorticoid-like effect (ex. megesterol)
27
Q

2 adrenal insuff

clinical manifestations

A
  • n/v
  • fatigue/weakness
  • lightheadedness/confusion
  • hypotension
  • fever
  • hypoglycemia
  • hypoNa (bc glucocorticoid def, NOT mineralocorticoid def)
  • NOT hyperpig
28
Q

2 adrenal insuff

dx/tx

A

dx

  • stimulation tests
    • ACTH (cortrosyn) stim test
    • insulin tolerance test
  • adrenal insufficiency with decr ACTH

tx

  • pharma
    • clucocorticoid replacement
29
Q

HTP axis

normal

A

hypothalamus-pituitary-thyroid axis

  1. hypothalamus releases TRH (+), somatostatin (-)
  2. pituitary releases thyrotropin
  3. thyroid releases T3 and T4

negative feedback:

  • T3 and T4 exert neg feedback on hypothal and pit
30
Q

neuroendo causes of thyroid disease

secondary hyper/hypothyroidism

A

note both involve TSH/T4/T3 going in SAME DIRECTION

secondary hyperthyroidism

  • RAREST secretory pit tumor
  • incr TSH, T4, T3
  • tx: pit surgery/rad/pharma

secondary hypothyroidism

  • usually pit lesion
  • decr TSH, T4, T3
    • labs similar to sick euthyroid symdrome
  • tx depends on cause…pit surg and thyroid hormone replacement
  • ***before relacing thyroid, want to make sure pt doesnt have BOTH thyroid def and adrenal insufficiency!
    • thyroid hormone controls metabolism BUT in context of person with adrenal insuff…if you restore thyroid hormone, the remaining cortisol is goign to be metabolized faster! could make adrenal insuff worse! → adrenal crisis
31
Q

prolactin axis

A

prolactin is not stimulated - it is CONSTITUTIVELY INHIBITED via DA secretion from hypothal

sooo, block DA → prolactin released

32
Q

causes of hyperprolactinemia

A
  • microprolactinoma (<200)
  • macroprolactinoma (>200)
  • pit stalk compression
  • meds which interfere with DA pathways (antipsychs)
  • primary hypothyroidism
    • TRH → TSH and prolactin secretion
  • pregnancy
33
Q

hyperprolactinemia

clinical manifestations

tx

A

elevated PRL → inhibited GnRH release → decr gonadotropins

  • similar clinical manifestations as hypogonadism
    • galactorrhea
    • oligomenorrhea/amenorrhea
    • infertility
    • gynecomastia
    • osteoporosis

tx

  • PRL-secreting adenomas → first line tx = PHARMA
    • bromocriptine (short acting DA agonist)
    • cabergoline (long acting DA agonist)
34
Q

PRL deficiency

A

inability to lactate

consider/evaluate…

  • panhypopituitarism
  • eval other pit axes

M2 Endo/Repro (20 decks)

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