Pituitary Dysfunction Flashcards
Anterior pituitary secretes which H?
6 hormones
Posterior pituitary secretes which H?
ADH (vasopressin)
Oxytocin
Higher CNS centers in pituitary gland regulation
Thalamus
Limbic system
RAS
Retina
Growth Hormone stimulatory factors
Sleep
Stress
Ghrelin
Protein/Arginine
HYPOglycemia
Growth H Inhibitory factors
Obesity/FFA
Glucocorticoids
Leptin
HYPERglycemia (OGTT to test for GH excess prod)
Excess H results in what?
- GH
- PRL
- ACTH
- TSH
- ADH
- GH - Acromegaly
- PRL - hypogonadism
- ACTH - Cushing’s disease
- TSH - Hyperthyroidism
- ADH - SIADH
Deficiency in H results in what?
- PRL
- FSH/LH
- ACTH
- ADH
- PRL - Failed lactation
- FSH/LH - Hypogonadism
- ACTH - Adrenal insufficiency
- ADH- Diabetes Insipidus
Hypothalamic-Pituitary - Target organ defect
Peripheral:
Primary disorder
- Target organ
Central:
Secondary Disorder
- Pituitary gland
Tertiary Disorder
- Hypothalamus
Hormone excess is assessed by _______ test.
Hormone deficiency is assessed by ______ test
Suppression test
- OGTT for GH suppression to confirm acromegaly
(give them glucose, hyperglycemia should inhibit GH)
Stimulation test
- Insulin tolerance test to eval ACTH and GH reserves
GH regulation
GHRH +
Somatostatin -
GH is pulsatile and acts at level of liver (Insulin-like growth factor: IGF-1)
Actions of GH
Acts on IGF-1 hormone
- Increase blood glucose
- Increase bone and cartilage mass/growth
- Increase protein synth/muscle mass
- Increase fat breakdown, TGA levels
- Increase Salt/H2O
Problems of GH excess
Gigantism:
- GH excess b4 puberty
(b4 closure of growth plates)
Acromegaly:
- GH excess after puberty
(after completion of linear growth)
*Elevated IGF-1 found, then do pituitary MRI (detected in >80% acromegaly)
Clinical presentation of Acromegaly (6)
- Acral/gacial changes
- HA
- Hyperhidrosis
- Oligo/Amenorrhea
- Obstructive sleep apnea
- HTN
Tx for acromegaly
- surgery
- medical
- somatostatin analog
- GH receptor antagonist - radiation therapies
Manifestations of adult growth hormone deficiency (GHD)
- Body composition
- Increased Fat deposition
- Decreased muscle mass, strength, exercise capacity - Bone strength
- increased bone loss and fracture risk - MEtabolic and cardiovascular effects
- Increased cholesterol levels
- increased inflamm and prothrombotic markers (CRP) - Psycological well being
- Impaired E and mood
- Quality of life
Dx of adult onset GHD (AoGHD)
Gold standard:
Insulin induced hypoglycemia
*Central adrenal insufficiency dx too
contraindications: elderly, h/o seizure disorder, CAD, or cerebrovascular disease
IGF-1 lvls are low
Stimulants of Lactotropes (and ultimately producing prolactin)
E2, TRH, Suckling,
DA is inhibitory
Causes of hyperprolactinemia
- Physiological
- Pregnancy, suckling, sleep, stress - Pharmacological
- Estrogens
- Antipsychotics, antidepressants, anti-emetics, opiates - Pathological
- Pituitary stalk interruption
- Hypothyroidism, chronic renal failure/liver failure, seizure
- prolactinoma
Prolactinoma common findins
at least 5 each
females 10: males 1
women:
- galactorrhoea
- menstrual irregularity
- infertility
- Impairs GnRH pulse generator
- MICROadenomas
men:
- galactorrhoea
- visal field abnormalities
- HA
- Impotence
- EOM paralysis
- anterior pit. malfxn
- MACROadenomas
Primary fxn of cortisol
- gluconeogenesis
- breakdown of fat and protein for glucose prod.
- control inflammatory rxns
*BIGFIB (319)
Complications in chronic cortisol excess
- changes in carb, prot, and fat metab
- peripheral wasting of fat/muscle
- central obesity, moon facies, fat pads
- osteoporosis
- diabetes
- hypertriglyceridemia - Changes in sex hormones
- amenorrhea/infertility
- excess hair growth
- impotence - salt and water retention
- HTN + edema - Impaired immunity
- Neuro cognitive changes
*BIGFIB (319)
Two types of cortisol excess
- ACTH dependent (70-75%)
2. ACTH Independent (25-30%)
Specific Signs and sx of CUshings syndrome
5
- Plethoric/moon facies
- Wide violaceous striae
(Abdominal, axillary) - Spontaneous ecchymoses
- Proximal muscle weakness
- early/atypical osteoporosis
(atraumatic rib fracture)
Is most cortisol bound or unbound?
bound - to transcortin
cortisol binding globulin - CBG
Screening test for Cushings syndrome
- midnight salivary or serum cortisol
for disrupted circadian rhythm
Pseudo-Cushing’s disease
- what is it?
- what can cause it? (6)
overactivation of HPA axis without tumorous cortisol hypersecretion
- severe depression,anxiety/OCD
- Severe obesity
- Obs. Sleep apnea
- Alcoholism
- Poorly controlled DM
- physical stress
Cushing’s disease work up
Plasma ACTh lvls are high-nl to mildly elevated –>
Pituitary MRI (microadenomas) –>
Inferior petrosal sinus sampling
Secondary/Tertiary Adrenal Insufficiency (AI)
suppression of HPA axis
- Exogenous glucocorticoid use (most coommon)
> 5-7.5 mg predisone
Central adrenal insufficiency test
Basal test
- random am cortisol level 18 then exclude dx)
Stimulation tests:
- GOLD std: Insulin-induced hypoglycemia
(assesses entire hypothalamic-pituitary-adrenal axis)
*Dx of adult onset GHD (AoGHD)
Hypogonadotropic hypogonadism is due to ______
Low FSH/LH
- Hypothalamic/pituitary diseases
- macroadenomas, prolactinomas, XRT
- Isolated GnRH deficiency
- Hemochromatosis - Fxnal deficiency
- critical illness
- OSA
- Starvation
- Meds-opiates
- glucocorticoids
Clinical features of hypogonadism in females (6)
- Anovulatory cycles
- oligo/amenorrhea, infertility - vagina dryness, dyspareunia
- Hot flashes
- Decreased libido
- Breast atrophy
- Reduced bone mineral density BMD
Clinical features of hypogonadism in males (6)
- Reduced libido
- Erectile dysfxn
- Oligospermia or azoospermia
- Infertility
- Decreased muscle mass, testicular atrophy, decreased BMD
- Hot flashes with acute and severe onset of hypogonadism
LH/FSH (gonadotropin) excess
Gonadotrope adenomas (FSH/LH) tumors are clinically silent
Middle aged pts with macroadenomas and related mass effects
(HA, vision loss, cranial nerve palsies, pituitary hormone deficiency)
Apoplexy
Clinical syndrome of HA, vision changes, ophthalmoplegia,
altered mental status caused by the sudden hemorrhage or infarction of the pituitary gland
Hypopituitarism
- types
- etiologies
Deficiency of 1 or more pituitary hormones
Panhypopituitarism = loss of all pituitary hormones
Etiologies:
- congenital genetic diseases
- Acquired pituitary lesions and/or treatments (75%)
Clinical syndromes of posterior pituitary gland are primarily associated with ______
disorders of AVP
AVP = ADH
release is controlled by HIGH osmolar states or
HYPOvolemia
Mechanism of ADH action
AVP binds to V1:
vascular vasoconstriction + platelet aggregation
AVP binds to V2:
antidiuretic effects in kidney
Adenylate cyclase activation –> movement of aquaporin water channels to the cell membrane –> water reabsoprtion
SIADH
syndrome of inappropriate AVP release/action in the absence of physiologic osmotic or hypovolemic stimulus
Most frequent cause of HYPOnatremia
Hallmark: excretion of inappropriately [urine] in the setting of hypo-osmolality and hyponatremia
SIADH dx
Hyponatremia (
SIADH tx
- Identify and reverse underlying disorder
- If mild-mod hyponatremia (120-134):
- water restriction (500-1000mL/24 hrs)
- V2 receptor antagonish
Risk of hyponatremia correction in chronic hyponatremia
Diabetes Insipidus
A syndrome of hypotonic polyuria as a result of:
- inadequate ADH secretion or
- Inadequate renal response to ADH
Hallmark: voluminous dilute urine (getting up at night)
Confirm polyuria with 24 hr urine volume collection
Classic triphasic response related DI
- DI-polyuric phase due to axonal shock/decreased AVP release (days 1-5)
- SIADH from degenerating neurons/excessive AVP release (days 6-11)
- Permanent DI after depleted ADH stores and if >80% AVP neuronal cell death
