Pituitary Gland and Hypothalamus Flashcards
hypothalamus - anatomy
*located in brain at the intersection of cortex, cerebellum, and brainstem
hypothalamus - functions
*maintains homeostasis by coordinating endocrine and nervous system to regulate:
1. thirst
2. reproduction
3. stress
4. autonomic function
5. energy/metabolism
6. appetite
7. temperature
8. blood pressure
9. circadian rhythm
hypothalamus - embryology
*derived from the diencephalon (from the forebrain/prosencephalon)
hormones produced by the hypothalamus
- releasing hormones:
-TRH, GHRH, GnRH, CRH
-target tissue = anterior pituitary - inhibitor hormones:
-dopamine (prolactin inhibiting factor)
-somatostatin (growth hormone inhibiting factor)
-target tissues = anterior pituitary (both) and GI tract (somatostatin)
pituitary gland - anatomy
*has anterior and posterior portions, with a thin intermediate lobe between
*located outside the dura, below the optic chiasm in the sella turcica; can be accessed through the back of the nose (sphenoid bone)
*pituitary stalk (infundibulum) passes through the dura, connects hypothalamus & pituitary gland
anterior pituitary gland - embryology
*aka adenohypophysis
*derived from Rathke’s pouch, ectoderm from the roof of the developing mouth (epithelial in origin)
*glandular tissue; can PRODUCE hormones
posterior pituitary gland - embyrology
*aka neurohypophysis
*derived from an evagination of diencephalon: neuroectoderm
*neural tissue; STORES hormones
clinical correlation of pituitary gland embyrology
*oral ectoderm (Rathke’s pouch) travels upward and diencephalon moves down to form the pituitary gland
*apoptosis occurs at base of Rathke’s pouch
note - persistence of Rathke’s pouch may result in craniopharyngioma
craniopharyngioma - overview
*most common supratentorial tumor of childhood
*occurs due to persistence of Rathke’s pouch during embryogenesis
*often contains calcifications
*can interfere with the pituitary’s ability to secrete hormones (hypopituitarism)
hypothalamic & pituitary circulation: hypophyseal portal system
- hypothalamus releases hormones into primary capillary plexus, which then travel to secondary capillary plexus in anterior pituitary
- long hypothalamic neurons trigger release of hormones (ADH and oxytocin) stored in the posterior pituitary into a capillary plexus
- lack of blood-brain barrier around neuroendocrine structures near ventricles allows for rapid hormone transport and tight regulation
vulnerability of anterior pituitary gland to hypotension
*anterior pituitary gland lacks direct arterial blood supply → increased risk of INFARCTION in the setting of hypotension
anterior pituitary - composition
composed of many cells:
*somatotrophs → produce GH
*lactotrophs → produce prolactin
*corticotrophs → produce ACTH
*gonadotrophs → produce FSH, LH
*thyrotrophs → produce TSH
hypopituitarism - overview
*refers to under-secretion of one or more pituitary hormones:
*the hormones most critical to sustain life are cortisol (regulated by ACTH) and thyroid hormones, T3/T4 (regulated by TSH)
*acute treatment = screen for and treat cortisol and thyroid hormone deficiency
*if present, could also treat ADH, gonadotropin, and growth hormone deficiencies, but these hormones are not essential for life
hypopituitarism - potential causes
*secretory or non-secretory pituitary adenoma, craniopharyngioma, brain injury, radiation
*Sheehan syndrome, empty sella syndrome, pituitary apoplex, medication-induced
Sheehan syndrome - overview
*ischemic infarct of the pituitary following postpartum hemorrhage
*susceptible from physiologic pregnancy-induced pituitary growth
*presentation: failure to lactate, amenorrhea, cold intolerance, hypotension, shock, hyponatremia
recall - a potential cause of hypopituitarism
empty sella syndrome (overview)
*radiologic finding in which the sella turcica looks empty (filled with CSF) from flattening or atrophy of the pituitary gland
*pituitary may secrete hormone per usual (no atrophy)
*often idiopathic, common in obese females, associated with idiopathic intracranial hypertension
recall - a potential cause of hypopituitarism
pituitary apoplexy - overview
*sudden hemorrhage of the pituitary gland, usually in the presence of pre-existing pituitary adenoma
*severe, sudden headache, vision changes (bitemporal hemianopsia, diplopia), hypotension, shock
recall - a potential cause of hypopituitarism
medication-induced hypopituitarism - overview
*monoclonal antibody checkpoint inhibitors used in oncology (ipilimumab, pembrolizumab)
recall - a potential cause of hypopituitarism
anterior pituitary hormone families
anterior pituitary hormones are peptide hormones with certain hormones sharing structural components:
1. LH, FSH, TSH hormones: heterodimeric glycosylated proteins with alpha and beta subunits
2. ACTH and MSH are derived from a common proopiomelanocortin (POMC) precursor
3. growth hormone and prolactin are structurally similar
anterior pituitary hormone families: FSH, LH, and TSH shared features
*the alpha subunit is shared/common (identical)
*the beta subunit determines hormone specificity
clinical correlation: high levels of hCG can stimulate TSH receptors and cause hyperthyroidism
prolactin - overview
*non-steroid hormone
*receptor = nonreceptor tyrosine kinase (JAK/STAT)
*produced by anterior pituitary
*structurally homologous to growth hormone
*main function = promotes lactation
*cleared by the kidneys
prolactin - functions
*promotes LACTATION:
-promotes mammary gland tissues development, duct proliferation and branching, and initiation of mild production by alveolar cells
-maintains milk production in response to nursing
prolactin - regulation
*prolactin secretion is continually inhibited by dopamine
*dopamine agonists → INHIBIT prolactin secretion
*dopamine antagonists/inhibitors → STIMULATE prolactin secretion
factors that INCREASE prolactin secretion
- dopamine inhibition / dopamine antagonists
- infant crying, nursing, nipple stimulation, chest wall injury
- high estrogen levels in pregnancy; estrogen therapy
- TRH
factors that INHIBIT prolactin secretion
- dopamine / dopamine agonists
- prolactin itself (increases dopamine)
- progesterone (blocks receptors at breast during pregnancy)
hyperprolactinemia - causes
- physiologic causes: pregnancy; nipple stimulation, chest wall trauma
- pathologic causes: prolactinoma; non-functioning adenoma or other tumor pressing on pituitary stalk; hypothyroidism
- medication ADEs: risperidone, phenothiazines, haloperidol, estrogen
- renal dysfunction
- idiopathic
top 3 causes of hyperprolactinemia
- pregnancy
- prolactinoma
- medication side effects (from dopamine antagonists: decreased dopamine → increased prolactin secretion)
hyperprolactinemia - symptoms
- premenopausal female symptoms: galactorrhea, infertility, amenorrhea
- male symptoms: gynecomastia, infertility, reduced libido, erectile dysfunction
note - can also have visual impairment, if the problem impacts the optic chiasm (near pituitary gland)
prolactinoma - overview
*a pituitary adenoma characterized by over-proliferation of lactotroph cells of the anterior pituitary gland
*similar presentation as other causes of hyperprolactinemia, PLUS: MASS EFFECT:
-bitemporal hemianopsia from compression of the optic chiasm
-cranial nerve palsies, if adenoma is large enough
*pituitary adenoma may co-secrete hormones
hyperprolactinemia - indications for treatment
*amenorrhea: goals of treatment = restore fertility and estrogen levels; low estrogen is detrimental to bone health for men and women
*galactorrhea
hyperprolactinemia - treatment
*dopamine agonists: cabergoline, bromocriptine
*effect: prolactin secretion is inhibited by dopamine
hypoprolactinemia - overview
*low prolactin levels
*symptoms: lactation difficulty
*usually due to anterior pituitary dysfunction: mass, infarction
*screen for other hormone deficiencies
*treat underlying cause, if possible (e.g. mass)
*no commercially available prolactin hormone replacement currently
posterior pituitary - overview
*an extension of axons of paraventricular and supraoptic nuclei that extend from the hypothalamus
*posterior pituitary stores oxytocin and antidiuretic hormone (produced by paraventricular and supraoptic nuclei) in vesicles until releasing these hormones in response to action potentials
oxytocin - overview
*produced in paraventricular (SAD POX) and supraoptic nuclei of the hypothalamus
*carried by neurophysin I via axons to posterior pituitary, where it is released
*receptors in brain, breasts, uterus
*uses a POSITIVE feedback loop
*acts via G protein-coupled receptor (subunit q) using PLC, DAG, IP3, PKC signaling pathways
oxytocin - functions
*causes uterine contractions during labor
*responsible for milk let-down reflex in response to suckling
*modulates fear, anxiety, social bonding, maternal-infant bonding, mood, and depression
oxytocin - regulation
*stimulated by:
1. infant crying and feeding: causes milk let-down and ejection via contraction of myoepithelial cells
2. cervical/vaginal stretch: causes uterine myometrial contraction to facilitate labor
-pharmacologic implication: used to induce labor and control post-partum hemorrhage
*uses a POSITIVE feedback loop (oxytocin leads to more oxytocin)
note - prolactin stimulates milk production, while oxytocin stimulates milk letdown (ejection from breast)
antidiuretic hormone - alternate names
*ADH
*vasopressin
*arginine vasopressin (AVP)
antidiuretic hormone - overview
*made in supraoptic (SAD POX) and paraventricular nuclei in the hypothalamus
*carried by neurophysin II down axons to be stored in posterior pituitary, where it is released
antidiuretic hormone - regulation
*secretion is stimulated by:
1. increased plasma osmolality (detected by osmoreceptors)
2. hypovolemia / decreased blood volume (detected by baroreceptors)
3. increased Ang II
antidiuretic hormone - functions
*regulates blood pressure and serum osmolality
*serum osmolality regulation: increased ADH → increased water reabsorption from urine → decreased serum osmolality (increased urine osmolality) and increased blood volume
antidiuretic hormone - mechanism of action
*ADH binds V2 receptors (Gs subunit GCPRs) on collecting ducts in kidney → activation of adenylyl cyclase → cAMP-mediated phosphorylation of aquaporin 2
*aquaporins (water channels) translocate to luminal membrane and facilitate water reabsorption in the collecting ducts
AVP deficiency and AVP resistance (central and nephrogenic diabetes insipidus)
*causes: decreased ADH levels (central) or lack of response to ADH (nephrogenic)
*effect: inability to reabsorb water → excess loss of water in urine
*clinical findings: profound polyuria & polydipsia; dehydration/hypovolemia; mental status changes
*lab findings: hypernatremia, high serum osm, low urine osm, low urine specific gravity
causes of AVP-deficiency (AVP-D, central diabetes insipidus)
*insufficient ADH production
*look for a history of: pituitary surgery, CNS tumor, head trauma, autoimmune diseases, other hormone deficits, Langerhan’s cell histiocytosis, rare genetic causes
treatment of AVP-deficiency (AVP-D, central diabetes insipidus)
*replace the hormone: arginine vasopressin (DDAVP)
*rehydrate
diagnosis of AVP-deficiency (AVP-D, central diabetes insipidus): water deprivation test
*no change or slight increase in urine Osm (don’t have any ADH, so they can’t concentrate their urine)
diagnosis of AVP-deficiency (AVP-D, central diabetes insipidus): desmopressin (DDAVP) administration
*significant increase in urine Osm (giving synthetic ADH allows them to concentrate their urine, b/c this is what they are missing)
causes of AVP-resistance (AVP-R, nephrogenic diabetes insipidus)
*insufficient renal response to ADH
*can be due to:
-V2 receptor mutation or AQP2 mutation
-obstructive uropathy
-hypercalcemia
-drug side effect (lithium, democlocycline)
-genetic causes
treatment of AVP-resistance (AVP-R, nephrogenic diabetes insipidus)
*treat the underlying cause
*diuretics: HCTZ
*rehydrate
diagnosis of of AVP-resistance (AVP-R, nephrogenic diabetes insipidus): water deprivation test
*minimal change in urine Osm
diagnosis of of AVP-resistance (AVP-R, nephrogenic diabetes insipidus): desmopressin administration
*minimal change in urine Osm (b/c they cannot respond to the ADH, regardless of giving them DDAVP)
primary polydipsia - overview
*excessive water intake
*causes: psychiatric illness, hypothalamic lesion
*serum Osm: low
*ADH level: low/normal
*water restriction test = increase in urine Osm
*treatment = water restriction
syndrome of inappropriate ADH (SIADH) - overview
*too much ADH → too much water retention
*clinical findings:
-hyponatremia (mental status changes, seizures, nausea, vomiting)
-low urine output
-labs: low Na+, low plasma Osm, high urine Osm
syndrome of inappropriate ADH (SIADH) - causes
*paraneoplastic syndrome (small cell lung cancer producing ADH)
*pulmonary disease (pneumonia, TB, COPD)
*CNS disease
*medications: SSRIs, carbamazepine, etc
*other endocrine disease (hypothyroidism, hypocortisolism)
syndrome of inappropriate ADH (SIADH) - treatment
*fluid restriction in stable patients; find/treat the underlying cause
*if symptomatic, severe hyponatremia, use:
-hypertonic saline
-ADH antagonists (tolvaptan)
-demeclocycline
-loop diuretics
*go slowly to avoid osmotic demyelination syndrome!
