Hypothalamus/Pituitary Flashcards
Pituitary development and anatomy
anterior (adenohypophysis): derived from ectoderm
posterior (neurohypophysis): derived from floor of diencephalon (hypothalamus); maintains connection to hypothalamus via pituitary stalk
located in bony sella turcica (laterally bounded by cavernous sinus, anterioinferiorly bounded by sphenoid sinus, superiorly lies optic chiasm)
vessels (hypophyseal portal system) delivers hypothalamic releasing hormones to the anterior pituitary
pituitary Corticotropin (ACTH)
- Regulated by Corticotropin-Releasing Hormone (CRH) from hypothalamus
- The target organ is the adrenal glands, stimulating cortisol synthesis and secretion
- Cortisol has a negative feedback on ACTH secretion (and some on CRH)
- Excess leads to Cushing’s syndrome
- Deficiency leads to secondary adrenal insufficiency
Pituitary Thyroid Stimulating Hormone (TSH)
- Regulated by Thyrotropin-Releasing Hormone (TRH)
- The target organ is the thyroid gland, stimulating thyroid hormone synthesis and secretion
- Thyroid hormones have a negative feedback on TSH secretion
- Excess leads to central hyperthyroidism
- Deficiency leads to central hypothyroidism
Pituitary Growth Hormone (GH)
- Regulated by Growth Hormone-Releasing Hormone (GHRH) and Somatostatin (-) from hypothalamus
- The target organs are multiple tissues (bone, cartilage, muscles…..), mainly through the action of IGF1(synthesized in the liver)
- IGF1 has a negative feedback on GH
- Excess leads to gigantism or acromegaly
- Deficiency leads to growth retardation or an adult clinical syndrome
Pituitary Gonadotropins (LH/FSH)
- LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone)
- Regulated by Gonadotropin-Releasing Hormone (GnRH) from hypothalamus
- The target organs are the testes and ovaries, leading to testosterone secretion and spermatogenesis in males, as well as estradiol secretion and gametogenesis in females
- Excess leads to precocious puberty
- Deficiency leads to hypogonadism
Pituitary Prolactin (PRL)
- Regulated by dopamine (tonic inhibition)
- The target organ is the breast (mammary glands), leading to initiation and maintenance of lactation
- Excess leads to galactorrhea and amenorrhea
- Deficiency leads to the inability to lactate after delivery
**only hormone under tonic inhibition!
Posterior Pituitary ADH (vasopressin)
- Regulated mainly by plasma osmolality and “effective” circulating blood volume
- The target organ is the collecting tubule, leading to increase in water permeability
- Excess leads to SIADH (Syndrome of Inappropriate Secretion of Antidiuretic Hormone)
- Deficiency leads to central diabetes insipidus
Posterior Pituitary Oxytocin
- Regulated by neurotransmitters (cholinergic, a-adrenergic)
- The target organs are:
- Breasts
- uterus
Role:
- Milk let-down reflex
- Uterine contractions during labor
Causes of cushings syndrome:
-ACTH-dependent
ACTH-independent
Pseudo-cushings
ACTH-dependent:
- cushing’s disease
- ectopic ACTH
- Ectopic CRH
ACTH-independent:
- adrenal adenoma
- adrenal carcinoma
- micronodular hyperplasia
- macronodular hyperplasia
Pseudo-cushings
- Major depressive d/o
- alcoholism
signs and symptoms of cushing’s disease
- centripetal obesity
- Moon facies
- buffalo hump
- hirsutism
- hyperpigmentation due to ACTH excess
Sx: centripetal obesity, glucose intolerance, proximal muscle weakness, HTN, hirsutism, hyperpigmentation, tinea versicolor infection
Tests?
- Positive Urine free cortisol
Identfiying Etiology?
- plasma ACTH=30
- Cortisol suppressed with high dose dexamethasone test
Dx?
Tx?
Tests:
- 24h Urine free cortisol collection: diagnostic if >3x normal, best screening test
- overnight low dose dexamethasone suppression test: postiive if pt does not suppress 8am cortisol to <1.8ng/dl
- salivary cortisol at midnight: positive if cortisol elevated
Etiology: determine ACTH dependency
-plasma ACTH
- <5pg/ml–> adrenal cushings–>CT scan adrenals
- >20pg/ml–>pituitary or ectopic cushings
- between 5-20: not definitive
-pituitary vs ectopic cushings:
- high dose dexamethasone suppression test: pts with pituitary cushings will be able to suppress ACTH secretion but ectopic will not
- petrosal sinus sampling: pituitary cushings will have high ACTH
Dx: Pituitary Cushings’ disease
Tx: surgical resection
Sx: Acral enlargement / Facial changes / Heel pad thickness \> 22 mm, Prognathism / Malocclusion, Arthralgias / Carpal tunnel syndrome, Excessive sweating Skin tags / Greasy, oily skin, Hypertension and Diabetes Sleep apnea (obstructive)
Tests?
- positive IGF-1
- Positive OGTT
Dx?
Tx?
Tests:
- IGF-1 (Somatomedin C) : high; Best screening test
- Failure of GH to suppress after OGTT (Oral Glucose Tolerance Test): Gold standard test (In acromegalics, GH does not suppress to < 1 ng/ml)
- If testing positive => MRI of pituitary (usually macroadenoma)
Dx: Acromegaly due to excess GH
Tx:
- transphenoidal surgery (curative 50%)
- if not cured by sugery use: somatostatin analog (octreotide), radiation, GH receptor antagonists
- screen for colon polyps/cancer
long term consequences of acromegaly
- arthropathy
- neuropathy
- CV disease–cardiomyopathy
- hypertension
- respiratory disease–airway obstruction
- malignancy–colon polyps
- Carbohydrate intolerance–Diabetes, IGT
Female Sx: amenorrhea, infertility, galactorrhea
Male Sx: decreased libido, impotence, headache/vision changes (mass effect)
Tests: abnormal pituitary MRI w/?
Dx?
Tx?
Tests: high prolactin with abnormal pituitary on MRI
Need to exclude other etiologies:
- Nonfunctioning pituitary macroadenoma with compression of the stalk (will show on MRI)
- Infiltrative diseases of the hypoth/pituitary axis (sarcoid, histiocytosis X etc)
- Primary hypothyroidism (high prolactin)
- Renal failure, Cirrhosis (can’t excrete prolactin)
- Pregnancy, Stress (ammenorhic women, send for pregnancy test)
- Drugs: Dopamine antagonists (mainly antipsychotics)
Dx: prolactinoma
Tx: almost always medical!
- Dopamine agonists: bromocriptine (Parlodel) or cabergoline (Dostinex)
- surgery reserved for pts not responding to drugs
Thyrotrope adenoma
clinical presentation?
treatment?
-Secreting TSH
-Rare: less than 1% of all pituitary tumors
2 clinical presentations:
- Hyperthyroidism with classic symptoms, goiter, high T4/T3 but inappropriately normal or elevated TSH (Remember: in primary hyperthyroidism, TSH is suppressed)
- Mass effects: headache, abnormal visual fields
Treatment: Surgery
GONADOTROPE ADENOMA
clinical presentation
treatment
- Secreting FSH (most common), LH or subunit
- Frequently referred to as “nonfunctioning” adenomas
- No obvious clinical endocrine syndrome from this hypersecretion
-2 clinical presentations:
- Mass effects: headache, abnormal visual fields
- Hypopituitarism (deficiency of other hormones from macroadenoma)
Treatment: Surgery
Sx: polyuria/polydipsia, likes iced drinks
Tests: polyura+ urine specific gravity 1.005 or less + urine osmolality of 200mmol/l or less
Determining Etiology?
Dx: diabetes insipidus due to insufficient secretion of ADH (central) or resistance of kidney to ADH (nephrogenic)
Etiology: Central DI responds to ddAVP and nephrogenic does not
Tx:
- central DI: ddAVP
- nephrogenic DI: NSAIDS
Causes of central DI
- Congenital (autosomal dominant)
- Acquired:
- Iatrogenic (following neurosurgery)
- Trauma
- Neoplasms (pituitary tumors, craniopharyngioma….)
- Ischemia (Sheehan’s syndrome)
- Granulomas (Sarcoidosis….)
- Infections (Tuberculosis…)
- Autoimmune
- Idiopathic
