Pituitary Flashcards
Where does the pituitary gland lie?
sella turcica
Where does the hypothalamus get its blood supply from?
superior hypophyseal artery -> internal carotid artery
Where does the pituitary gland get its blood supply from?
- anterior lobe -> long portal veins from the hypothalamus
- posterior lobe -> inferior hypophyseal artery
What are the hormones secreted from the anterior pituitary gland?
- Acidophils -> prolactin (TRH increases it & dopamine inhibits it) & Growth hormone
- Basophils -> all the rest (TSH, ACTH, FSH, LH)
- Chromophobes -> nothing
What are the hormones secreted from the posterior pituitary>
oxytocin & ADH
- synthesized in paraventricular & supraoptic nuclei of hypothalamus
What are the effects of pituitary tumors?
- endocrine effects -> according to hormones
- mass effects -> headache
-> superior extension
-> lateral extension: cranial 3, 4, 6 & ophthalmic division of 5 -> diplopia & facial pain
temporal lobe dysfunction
-> inferior extension: nasopharyngeal mass & CSF rhinorrhoea
-> posterior extension: bilateral pyramidal tract signs
What is the effect of the superior extension of a pituitary tumor?
- chiasmal syndrome -> decreased visual acuity & bitemporal hemianopia
- hypothalamic syndrome -> SIADH (early due to irritation)
- > disturbance of thirst, temp, appetite, & sleep regulation
- > DI (late due to destruction)
When is a prolactinoma discovered?
in females -> micro adenoma
in males -> macro adenoma (doesn’t manifest until its larger)
What is the clinical picture of a prolactinoma?
1- compression symptoms
2- in females
- amenorrhea & galactorrhea
- hypoestrogen symptoms -> decreased libido & vaginal secretions, dyspareunia
-> osteoporosis
- hyperadrenergic symptoms -> hirsutism & acne
3- in males
- decreased libido & impotence
- oligospermia & infertility
- gynecomastia (rare)
4- delayed puberty
What are the investigations that should be done for prolactinomas?
basal prolactin levels
- females -> 0-25ng/ml
- males -> 0-20ng/ml
plain xray, CT, MRI
- to find tumor
How is a pituitary tumor treated medically?
Bromocriptine 2-5 times a day (dopaminergic agonist) - CABERGOLIN once a week (more effective)
- decreases hyperprolactinaemia
- restores menstruation, fertility, & stops galactorrhea
- decreases the size of the tumor
(continued for 1 - 2 years)
What are the side effects of bromocriptine?
- short half life so taken 2-5 times a day
- nausea
- vomiting
- postural hypotension
If medical treatment fails, what should be done next?
if tumor is <10mm (micro adenoma) -> trans-sphenoidal surgery
if tumor is >10mm (macro adenoma) -> trans-frontal surgery
What are the complications of a trans-sphenoidal surgery?
- hypopituitarism
- CSF rhinorrhea
- meningitis
- optic nerve damage
What is the inhibitory hormone of the growth hormone?
somatomedins (synthesized in the liver)
What regulates the growth hormone?
STIMULATION (GHRH)
- hypoglycemia
- stress, exercise
- estrogen, clonidine, L-dopa
SUPPRESSION (somatomedins)
- hyperglycemia
- obesity
What are the effects GH hyper secretion?
acidophil pituitary adenoma
could lead to:
ACROMEGALY -> after fusion of epiphysis
GIGANTISM -> before fusion of epiphysis
What are the effects of gigantism?
- massive growth of skeleton
- soft tissue enlargement
- early -> patient is strong
- later -> weakness, hypogonadism, myopathy, peripheral neuropathy
What are the effects of acromegaly?
- enlargement of acral parts (hands, nose, feet, jaw)
- progressive between the 2nd & 4th decades (manifestations appear 10 - 20 years later)
What are the facial & soft tissue features of acromegaly?
Facial
- enlarged lips & nose
- enlargement of mandible -> prognathism & increased spacing of lower teeth
- macroglossia
- enlargement of frontal sinuses
- voice is cavernous & husky
Soft tissue
- increase ring, glove, shoe & hat size
- hands & feels are grossly enlarged (spade-like hands)
What are the neurological symptoms of acromegaly?
- entrapment neuropathy -> carpal tunnel syndrome
- peripheral neuropathy
- proximal myopathy
- mass manifestations
What are the cardiovascular & joint manifestations of acromegaly?
- HTN
- cardiomegaly
- Raynaud phenomena
- arrhythmias
- sleep apnea
- osteoarthritis of spine, knee, & hips -> late
What are the skin & metabolic manifestations of acromegaly?
SKIN
- hypertrichosis
- increased pigmentation -> acanthosis nigricans
- warm, moist, & thickened
METABOLIC
- secondary diabetes (glucose intolerance)
- hyperhidrosis -> increased metabolic rate
- hyperphosphatemia
- hypercalcemia
What will be found on x-ray of acromegaly patient?
SKULL
- thickening of cortex
- pneumatisation of frontal sinus
- prominent occipital protuberance
- frognathism & big mastoid process
- protrusion of the mandible
HANDS
- mushroom appearance (pseudo clubbing)
- brush border (tufting of terminal phalanges) -> periosteal thickening
HEEL -> thickening of heel pad >22mm
What will be found on ophthalmic exam of acromegaly patient?
- bitemporal hemianopia
- papilledema
- optic atrophy
- glaucoma -> if severe
What are the lab tests that should be preformed for diagnosis of acromegaly?
ENDOCRINAL
- suppression test: failure of GH suppression in response to oral glucose load (to <2ng/ml)
- IGF-1 levels increased (somatomedin)
- GHRH increased from bronchial carcinoid (ectopic)
METABOLIC
- increase BMR
- hyperglycemia
- hypercalcemia
What is the first line of treatment for acromegaly?
Surgical removal of acidophil pituitary tumor
When should medical treatment be done in cases of acromegaly?
- when surgery is contraindicated
- when in need for rapid relief of symptoms
Bromocriptine -> adjunctive therapy
Octreotide -> longer duration & more specific
-> side effect: vasoconstriction
Somatostatin -> very short half life & not specific for GH
What are the causes of hypopituitarism?
1- infarction of the pituitary -> Sheehan, vasculitis, DM
2- infection & granuloma -> TB, syphilis, meningitis, sarcoidosis
3- idiopathic (congenital) -> deficiency of pituitary hormones
4- neoplastic -> adenoma, craniopharyngioma, leukemia, lymphoma, metastasis
5- physical agents -> radiation, surgery, trauma
6- miscellaneous -> haemochromotosis
What is the most common cause of hypopituitarism?
POSTPARTUM NECROSIS (SHEEHAN SYNDROME) - anterior pituitary most susceptible because its enlarged in pregnancy without increased blood supply
What is the clinical picture of hypopituitarism in childhood?
PITUITARY DWARFISM (Levi-Laurain syndrome)
- idiopathic decrease in GH
- proportionate dwarfism
- childish face
- hypogonadism -> later
FROHLICH’S SYNDROME (dystrophia adiposgenetalis)
- due to tumor or functional hypothalamus disturbance
- dwarfism
- hypogonadism
- Samosa shaped obesity -> trunk & face only
- Genu Valgum
- hypothalamic disturbances -> DI, polyphagia, hypersomnia
LAURENCE-MOON-BIEDLE SYNDROME Fröhliches syndrome + - mental retardation + skull deformity - retinitis pigmentosa - polydactyly, syndactyly
What is the clinical picture of hypopituitarism in adults?
1- panhypopituitarism - Simmonds disease
2- ISOLATED HORMONE DEFICIENCY
- prolactin -> failure of lactation
- GH -> silent
- Gonadotropic hormones -> skin & sexual manifestations
- ACTH -> hypoglycemia, inability to withstand physical & psychic stress, low resistance to infections, Addison’s or Simmond’s disease
- TSH -> secondary hypothyroidism
3- general -> pressure manifestations
-> coma due to hypothermia, hypoglycemia, or pressure on brainstem or hypothalamus
What are the manifestations of gonadotropic hormones?
Skin
- fine & wrinkled
- loss of secondary sexual hair progeria
Sexual manifestations Men - decreased libido - testicular atrophy - oligospermia
Women
- vaginal dryness
- dyspareunia
- secondary amenorrhea
- infertility
- breast atrophy
What is the difference between Addison’s disease & Simmond’s disease?
ADDISON’S primary hypoadrenalism
- pigmentation due to stimulation of melanocytes
- ACTH is increased
- hypovolemia & hyperkalemia
SIMMOND’S secondary hypoadrenalism
- absent pigmentation (lack of lipoprotein) + pallor
- depigmentation of areola in females
- ACTH & all other pituitary hormones are decreased
How do we test for GH reserve?
- measure GH level during sleep & then after exercise -> if level is > 6 then normal reserve
if not > 6
1- insulin induced hypoglycemia (0.1 U/kg IV)
2- L-dopa
3- Clonidine test
samples are taken fasting & then at 60, 90mins -> if values are > 6 then normal
How is LH & FSH reserve tested?
normal gonadal function - to exclude hypothalamic or pituitary diseases - females -> normal menses - males -> normal sperm count if irregular 1- measure basal LH & FSH if low 2- LHRH (GnRH) test 3- Clomiphene citrate test (estrogen antagonist) -> doubling the baseline LH & FSH
How do we test for TSH reserve?
- TRH test -> doubling the basal TSH level -> if low then secondary hypothyroidism
How do we test the ACTH reserve?
- insulin induced hypoglycemia -> increases cortisol level >10
How is hypopituitarism treated?
- Surgery in space occupying tumors
- Radiotherapy if tumor is not entirely removed surgically or patient is unfit for surgery
- Hormone replacement
1- prednisone orally instead of ACTH (cortisol)
2- L-thyroxine
3- GH 3 injections BEFORE epiphyseal closure
4- Testosterone or estrogen & progesterone if fertility is NOT needed - Human menopausal gonadotropin (HMG) or human chorionic gonadotropin (HCG) if fertility is needed
what are the causes of pituitary apoplexy?
- hemorrhage in pituitary gland
- cerebrovascular accident
- sickle cell anemia
What is the clinical picture of pituitary apoplexy?
- sudden headache (increase ICT)
- meningeal irritation (pain)
- sudden decrease in anterior pituitary hormones -> autohypophysectomy
- Coma
What investigations should be done for pituitary apoplexy & how should it be treated?
CT -> diagnostic -> hemorrhage will be seen
CSF -> bloody
1- surgical decompression
2- dexamethasone should be given (glucocorticoids)
What are the general causes of short stature?
1- Primary defects -> in the skeletal system itself
2- Secondary defects -> systemic problems outside of the skeletal system
What primary defects could lead to short stature?
1- skeletal dysplasia
2- chromosomal abnormalities -> Down & Turner syndromes
3- Inborn error of metabolism
4- genetic short stature -> pygmies
What are the secondary defects that could lead to short stature?
1- intrauterine growth retardation -> infection, placental insufficiency, or maternal illness
2- idiopathic (most common)
3- malnutrition -> Kwashiorkor, marasmus
4- GIT diseases -> celiac, chronic liver, IBD, cystic fibrosis
5- renal diseases -> chronic parenchymal diseases, RTA
6- cardio-respiratory diseases -> Congenital heart diseases, asthma
7- endocrine diseases
8- psychological deprivation
What are the endocrinal diseases that lead to secondary short stature?
1- panhypopituitarism or isolated GH or GHRH insufficiency 2- pseudohypoparathyroidism 3- precocious puberty 4- Cushing syndrome 5- Cretinism
How should short stature be assessed?
1- clinical features of disease
2- physical examination
- height to weight ratio
- specific physical findings for each disorder
How can the height to weight ratio help us identify the diagnosis of short stature?
SHORT & UNDERWEIGHT
- malnutrition
- hypothyroidism
- systemic diseases
SHORT & OVERWEIGHT
- Cushing’s
- decreased GH (decreases basal metabolic rate)
What are physical findings of cretinism?
- dry skin
- coarse hair
- depressed nasal bridge
- big lips
- protruding tongue
What are physical findings of cushing’s syndrome?
- central obesity
- striae
- HPN
What are physical findings of Turner syndrome?
- webbed neck
- coarctation of the aorta
What are physical findings of pseudohypoparathyroidism?
- moon face
- obesity
- short metacarpals
- mental retardation
How is short stature diagnosed & treated?
normal average height = father’s height + mother’s height/2 +- 6cm
if less than that then
1- treat the cause as early as possible
2- if idiopathic -> give GH BEFORE PUBERTY
What are the effects of ADH (vasopressin) on the body?
- increases absorption of water in the collecting tubules
- vasoconstriction
What are the factors that increase ADH?
1- increased osmolarity
2- hypovolemia -> reflex stimulation due to decreased inhibitory impulses from the left atrium (less stretch)
3- hypotension -> baroreceptors are activated
4- higher centers stimulated by psychological factors & stress
5- pharmacological influence
What are the pharmacological agents that increase ADH?
1- acetylcholine 2- beta-adrenergic agonists 3- chlorpropamide 4- carbamazepine 5- cyclophosphamide 6- nicotine & morphine
all lead to oliguria
What are the pharmacological agents that decrease ADH?
1- diphenylhydantoin
2- naloxone
lead to polyuria
What are the types of diabetes insipidus?
- CENTRAL DI (pituitary or hypothalamus issue): low or absent ADH
- NEPHROGENIC DI: kidney unresponsive to ADH
both cause polyuria of low osmolarity urine
What are the causes of central DI?
1- FAMILIAL
- dominant inheritance
- recessive inheritance
- DIDMOAD (Wolfram syndrome)
2- ACQUIRED any destruction of pituitary
- trauma or tumors: in the brain
- idiopathic (most common)
- infections: meningitis, encephalitis
- infiltrations: sarcoidosis
- vascular: Sheehan syndrome
What are the causes of nephrogenic DI?
ALL ACQUIRED
1- electrolyte disturbance
- hypokalemia -> primary aldosteronism
- hypercalcemia -> hyperparathyroidism
2- drugs -> lithium
3- diseases of the kidney
- chronic renal failure
- acute tubular necrosis (renal failure)
4- systemic disorders
- amyloidosis
- sickle cell anemia (causes shrinkage of kidneys)
What is the clinical picture of DI?
- polyuria -> polydipsia
- dehydration -> weakness, prostration, low grade fever
What investigations are done to diagnose ADH insufficiency?
if patient is complaining of polyuria
1- exclude DM by glucose tests
2- urine analysis to confirm decreased ADH -> increase volume & decreased osmolarity
or stimulation tests
3- NaCl stimulation test
- normally -> increases osmolarity -> increases ADH -> oliguria
- if decrease in ADH -> no response
4- stimulation test by vasopressin (2-3 days IV)
- if still polyuria -> nephrogenic DI
- if oliguria -> either normal or central DI
or from the start
DEHYDRATION TEST
How is the dehydration test preformed?
normally
- dehydration -> increases ADH -> oliguria & increased osmolarity
- give ADH -> less volume (oliguria) but osmolarity is the same
Central DI
- dehydration -> no ADH -> polyuria & decreased osmolarity
- when u give ADH -> oliguria & increased osmolarity
nephrogenic DI
- dehydration -> increases ADH -> no response (polyuria & decreased osmolarity persist)
- when u give ADH -> no response (polyuria & decreased osmolarity persist)
How is central DI treated?
Hormonal replacement
- vasopressin -> S.C
- desmopressin (DDVAP) -> intranasal
- vasopressin tannate in oil -> intramuscular
or
Non hormonal (drugs that increase ADH)
- chlorpropamide
- clofibrate
- carbamazepine
How is nephrogenic DI treated?
TREAT THE CAUSE
&
give hydrochlorothiazide (diuretic that decreases sodium) -> hyponatremia -> decreased water excretion
What are the causes of SIADH?
increased ADH secretion & oliguria due to
- malignancy: pituitary tumors or bronchogenic carcinoma
- pneumonia, TB
- cerebrovascular accidents
- drugs: chlorpropamide, cyclophosphamide
- hypothyroidism, ACUTE PSYCHOSIS
What are the clinical findings in SIADH?
- weight gain -> edema
- lethargy, confusion, convulsion, coma: due to deceased osmolarity which leads to dilution hyponatremia + cerebral edema
- oliguria
What are the lab findings in SIADH?
- decreased PLASMA osmolarity (<270)
- increased URINE osmolarity (>100)
How is SIADH treated?
1- hypertonic saline infusion: increase in Na should not be more than 1-2ml/hr (to avoid cerebral dehydration)
2- restrict water intake
3- drugs that decrease ADH: diphenylhydantoin or naloxone
4- treat the cause
