Pituitary/Hypothalamus Flashcards
What is the embryologic origin of the neurohypophysis ?
Evagination of ventral hypothalamus and third ventricle
What is the embryologic origin of the adenohypophysis?
Rathke pouch (ectodermal evagination of the oropharynx)
What are the transcription factors involved in pituitary gland development?
- SOX3, HESX1, LHX3, LHX4, PIT1, PIT 2: common to all
- SF1: gonadotrops
- GATA2: gonadotrops and thyrotropes
- PROP1 and POU1F1: thyrotropes, lactotropes and somatotropes
- TPIT, LIF, NEUROD1: POMC/corticotropes
What organs/glands secrete somatostatin?
- Hypothalamus
- Pancreatic islet cells
- Gastrointestinal mucosa
- C cells (parafollicular cells of thyroid)
What part of the hypothalamus is the satiety centre? Hunger centre?
- Satiety centre = ventromedial hypothalamus
- Hunger centre = lateral hypothalamus
_____-frequency pulses of GnRH favour FSH release while _____-frequency pulses favour LH release
Low-frequency pulses of GnRH favour FSH release while high-frequency pulses favour LH release
What are the populations of neurons involved in feeding/hunger that are located in the arcuate nucleus?
- Neuropeptide POMC and CART (cocaine- and amphetamine-regulated transcript): inhibit food intake
- Neuropeptide Y and ARP (agouti-related peptide): stimulate food intake
The pineal gland secretes _____
Melatonin
What drugs stimulate prolactin release? Inhibit?
STIMULATE: Dopamine antagonists (phenothiazines, haloperidol, risperidone, metoclopramide, reserpine, methyldopa, amoxapine, opioids)
INHIBIT: Dopamine agonists (levodopa, apomorphine, bromocriptine, pergolide), GABA
TSH _______ with age and BMI
Increases
List 3 contraindications to the insulin hypoglycemia test
- Elderly patients
- Patients with cardiovascular/cerebrovascular disease
- Patients with epilepsy
- ?Pediatric patients
What is the metyrapone test used for?
- Assess adequacy of ACTH secretion
- Blocks 11-beta hydroxylase (last step in cortisol synthesis), which decreases cortisol and increases 11-deoxycortisol. This should stimulate ACTH secretion.
- Metyrapone may cause GI upset
What causes failure of GH suppression following a glucose load?
- Acromegaly
- Starvation
- Protein-calorie malnutrition
- Anorexia nervosa
How does obesity impact pituitary testing?
- GH seceretion is impaired to all stimuli (insulin-induced hypoglycemia, arginine, levodopa, glucagon, GHRH)
- Obesity causes hypogonadotropic hypogonadism in men
How does diabetes mellitus impact pituitary testing?
- Most patients with DM1 have normal/elevated GH levels that do not rise further in response to hypoglycemia or arginine
- IGF-1 levels are low despite elevated GH levels
How does uremia impact pituitary testing?
- Basal levels of GH, PRL, LH, FSH, TSH and free cortisol are elevated (prolonged half life)
- GH paradoxically increased following glucose administration
- GH is hyperresponsive to hypoglycemia stimulus
- Dexamethasone suppression of cortisol may be impaired
How does starvation/anorexia nervosa impact pituitary testing?
- GH secretion increases (may cause paradoxical increase in GH with glucose load)
- Low levels of gonadal steroids
- Cortisol levels increased, fail to suppress with dexamethasone
How does depression impact pituitary testing?
- Inability for dexamethasone to suppress plasma cortisol, elevated cortisol secretion
______ % of the population harbour nonfunctional and asymtomatic pituitary adenomas
10-20%
What is the sequence of aquired loss of pituitary hormones?
- GH
- FSH/LH
- TSH
- ACTH
- PRL
(Go Find The Adenoma Please)
List a differential diagnosis for hypopituitarism
- Invasive (ex. craniopharyngioma)
- Infarction (ex. Sheehan syndrome)
- Infiltrative (ex. Langerhans histiocytosis, sarcoidosis, hemochromatosis)
- Injury (ex. severe head trauma)
- Immunologic (ex. lymphocytic hypophysitis)
- Iatrogenic (ex. surgery/radiation)
- Infectious (ex. TB, syphilis, fungal)
- Idiopathic (ex. familial, septo-optic-dysplasia)
- Isolated pituitary hormone deficiency (various genetic causes)
(Nine I’s)
What is pituitary apoplexy?
- Spontaneous hemorrhagic infarction of a pituitary tumor (may also be related to diabetes mellitus, radiotherapy, or open heart surgery)
- Acute pituitary failure results
List 4 genetic conditions causing pituitary adenomas or hormone excess
- MEN1 syndrome (MEN1) - prolactinomas
- MEN4 syndrome (CDKN1B) - prolactinomas
- Familial isolated pituitary adenomas (AIP) - GH secreting tumors
- McCune-Albright syndrome (GNAS1) - GH hypersecretion
- Carney complex (PRKAR1) - GH hypersecretion
- X-linked acrogigantism (GPR101) - GH secreting tumors
- Cushing’s disease (USP8) - ACTH
- DICER1 (DICER1) - pituitary blastoma
- Familial hyperprolactinemia (PRLR)
- Pituitary adenomas (PTTG1) - all subtypes
- Craniopharyngioma (CTNNB1 or BRAF genes)
List 4 genetic conditions causing pituitary insufficiency
- X-linked congenital adrenal hypoplasia (NROB1)
- Early onset isolated ACTH deficiency (Tpit)
- Kallman syndrome (KAL1, FGFR1, FGF8)
- Combined pituitary hormone insufficiency (PROP1)
- Congenital hypopituitarism (POU1F1/Pit1)
- Other (LHX3, LHX4, PITX2, RPX)
