Disorders Of The Hypothalamus And The Pituitary

Front 1

How does one differentiate between clinical syndromes involving hypothalamus and pituitary tumors?

Back 1

hypothalamus involves diabetes insipidus, while pituitary tumors does NOT

Front 2

What is the effect of excessive prolactin secretion?

Back 2

directly and indirectly causes hypogonadism

Front 3

list four groups of disorders of the hypothalamus, give examples of each group

Back 3

1.) tumors (craniopharyngioma)
2.) inflammation (lymphocytic hypophysitis)
3.) infiltration (sarcoidosis and histiocytosis)
4.) metastatic tumor (breast and lung)

Front 4

There are 7 different causes of centrla diabetes insipidus. List them:

Back 4

1.) idiopathic (30-50%): autoimmune and inflammatory?)
2.) CNS/ pituitary surgery, trauma, anoxic encephalopathy
3.) primary tumors, craniopharyngiomas, suprasella germinoma, pinealoma
4.) metastatic tumors, leukemia, and lymphoma
5.) granulomatous disease like TB
6.) hereditary: AD onset at months to years
7.) pregnancy: unmasking partial central diabetes or nephrogenic insipidus/ markedly increased levels and activity of vasopressinase (oxytocinase)

Front 5

What are the three types of vasopressin receptors and their functions?

Back 5

V1a receptors mediated vasopressor activity
V1b receptors modulated ACTH secretion
V2 receptors mediate renal handling of water excretion and promote coagulation factor 8 action

Front 6

What are vasopressin V1 agonist uses?

Back 6

1.) treat systemic hypotension (septic shock)
2.) decrease splanchnic blood flow in upper GI hemorrhage (post BX, gastritis, ulcer)
3.) enhance coronary blood flow and myocardial oxygenation in cardiac asystole

Front 7

What are vasopressin V2 agonists used for?

Back 7

1.) decrease water excretion in central diabetes insipidus and nocturnal eneuresis
2.) increase circulating levels of factor 8 and improve platelet responsiveness (hemophilia A, VWD and uremic coagulopathy)

Front 8

what are two oral vasopressin receptor ANTAGONISTS?

Back 8

conivaptan and tolvaptan

Front 9

what is desmopressin/ what is it made of/

Back 9

DDAVP: desamino, d-arginine vasopressin: lack of amino at position 1 --> increase half life
L-arginine at position 8: changed to D-arginine

Front 10

what is the most frequent sellar tumor of childhood and adolescence?

Back 10

craniopharyngioma (3% of all tumors of brain)

Front 11

Where does craniopharyngioma arise and where is it most commonly located in the brain?

Back 11

-usually suprasellar but may extend into the sella
-arise from Rathke's pouch remnants extending into the diencephalon during development

Front 12

describe the histological and clinical presentations of craniopharyngioma:

Back 12

histology: cystic-solid cystic filled with lipid rich viscous fluid (consistency of motor oil)

childhood presentation: growth retardation, pubertal delay, visual field loss, vomiting

Front 13

What are four types of functional pituitary tumors?

Back 13

1.) excess growth hormone (acromegaly)
2.) pituitary dependent Cushing's disease (ACTH)
3.) prolactinomas with prolactin associated hypogonadism
4.) central hyperthyroidism due to TSH secretion

Front 14

list six types of pituitary tumors:

Back 14

prolactinoma, somatotroph adenoma, corticotroph adenoma, gonadotroph adenoma, null cell, thyrotroph adenoma

Front 15

prolactinoma: prevalence, hormone staining, and clinical manifestations

Back 15

40-45%;prolactin staining; signs of increased prolactin

Front 16

somatotroph adenoma: prevalence, hormone staining, and clinical manifestations

Back 16

20%; GH +/- prolactin; acromegaly

Front 17

corticotroph adenoma; prevalence, hormone staining, and clinical manifestations

Back 17

10-12%; ACTH +/- others; Cushing's disease

Front 18

gonadotroph adenoma; prevalence, hormone staining, and clinical manifestations

Back 18

15%; FSh, LH, alpha SU, beta SU: compression SX and hypopituitarism

Front 19

Null cell; prevalence, hormone staining, and clinical manifestations

Back 19

5-10% ; none; compression sx and hypopituitarism

Front 20

thyrotroph adenoma; prevalence, hormone staining, and clinical manifestations

Back 20

1-2%; TSH, alpha SU , +/- GH; hyperthyroidism and compression Sx

Front 21

pituitary syndromes; carney syndrome features: 5 groups of features list them:

Back 21

1.) punctate skin pigmentation, myxomas, testicular and adrenal tumors;
2.) multifocal somatommatropic hyperplasia; subclinical increases in hGH and hPR
3.) growth hormone secreting tumors for 10-20%
4.) mutation in subunit of PKA is possible
5.) localization to 17q22-24 +/- 50% and others: 2p16

Front 22

McCune albright syndrome 3 groups of features. list them:

Back 22

1.) patches of skin pigmentation and bone tumors
2.) adrenal tumors, precocious ovarian function; GH-secreting tumors
3.) inactivation of GTPase of Gsalpha with increased CAMP

Front 23

MEN I features:

Back 23

1.) loss of function in tumor suppressor gene men 1
pituitary tumor, hyperparathyroidism, pancreatic neuroendocrine tumors: PPP

Front 24

MEN type II (activating germ line mutation in RET proto-oncogene): type IIa

Back 24

-medullary cancer thyroid; hyperparathyroidism, pheochromocytoma

Front 25

MEN type II (activating germ line mutation in RET proto-oncogene): type IIb:

Back 25

(previously type III): marfanoid body habitus; medullary cancer thyroid; pheochromocytomas, mucosal gangliomatosis (no hyperplasia or pituitary tumors) ; familial isolated medullary thyroid carcinoma

Front 26

MEN type 4 features:

Back 26

-loss of function in gene CDKN1B encoding kinase p27 a regulator of G1/S2: pituitary tumor, hyperparathyroidism and other tumors (renal and testis)

Front 27

pituitary tumors: diffuse pituitary hyperplasia: 4 causes

Back 27

1.) pregnancy
2.) prolonged primary hypothyroidism or hypogonadism
3.) GHRH secreting tumors: eutopic (hypothalamic gangliocytomas) and ectopic: (extrahypothalamic; peripheral neuroendocrine tumors)

Front 28

what are features of a discrete pituitary tumor?

Back 28

-most common human neoplasm,
-malignancy is rare
-monoclonal origin except in rare conditions
-GSalpha (GSP) alteration in 40% of sporadic GH secreting neoplasm
-pituitary transforming gene expression is common!!!

Front 29

what are intrasellar manifestations of pituitary tumors?

Back 29

-headache and pituitary hypofunction

Front 30

What is the range of tumor associated loss in hormones for pituitary tumors?

Back 30

GH > LH/FSH > TSH > ACTH

Front 31

what are suprasellar manifestations of pituitary tumors?

Back 31

impingement on optic chiasm and obstruction of 3rd ventricle, hydrocephalus and altered sensorium

Front 32

List the lateral extension pituitary tumor manifestations:

Back 32

impingement on Cranial nerve 3,4,6

Front 33

what happens when there is inferior erosion of the pituitary tumors?

Back 33

spinal fluid leak and meningitis!

Front 34

What is the incidence and prognosis of pituitary incidentaloma:

Back 34

-prevalence on autopsy: 11% (90% stain for prolactin): MRI: 10%
-hormonal activity: none
management: prolactin measurement (normal by definition)
prognosis: < 0.5 % chance of significant clinical events/ need to measure prolactin ; < 5 mm no additional study but if 6-9 mm repeat over 2 years regularly

Front 35

What are the clinical effects in women of prolactinoma?

Back 35

-microadenomas are most common:
-infertility, oligomenorrhea, and occur in 20% of patients with amenorrhea

-galactorrhea: 30-40% of women with prolactinoma: 50% of patients with galactorrhea no increase in prolactin // uncommon with high levels of hPR secondary to hypogonadism

Front 36

What are the clinical effects of prolactinoma in men?

Back 36

-macroadenomas are most common;
-longstanding erectile dysfunction at presentation
-headaches, visual field impairment common
-hormonal deficiencies (TSH and ACTH)

Front 37

What are five causes of increased prolactin?

Back 37

1.) hypothalamic: diminished synthesis or release of dopamine (tumors, sarcoidosis; hemochromatosis)

2.) pituitary stalk impairment: impaired transport of dopamine (damage, compression, blood supply injury)

3.) lactotraph insensitivity to dopamine: drugs: dopamine receptor blocking effects: benzamides, butyrphrenones, phenothiazines

4.) increased lactotroph number or secretion: Tumor: pituitary tumor lactotroph or mixed/pluripotential; estrogen effects: pregnancy, drugs; increased TRH; chest wall injury

5.) decreased prolactin disposal (renal failure; and macroprolactinemia: rare molecular genetic variation)

Front 38

prolactin inhibitory factor (dopamine): what are the effects of lo, moderate, and high doses of the catechol neurotransmitter?

Back 38

1.) low dose: (203 mcg/min): dilates splanchnic bed and increases renal blood flow
2.) moderate dose (4-8 mcg/min): activates cardiac Beta-1 receptors to increase cardiac contractility
3.) high dose (>10 mcg/min) acts as a pressor by activating peripheral alpha receptors

Front 39

What receptors are coupled to G proteins and increase intracellular CAMP?

Back 39

D2 receptors; growth hormone secreting tumors may also express D2 receptors

Front 40

what happens to tumors when dopamine agonists are used?

Back 40

-dopamine agonists may have dramatic effect on prolactin secreting tumor; macroadenomas often shrink and decrease in size may be detectable within 24 hours
-microadenomas respond dramatically and often with resumption of menses and restoration of fertility

Front 41

What are two dopamine agonists?

Back 41

-bromocriptine: excellent drug with strong record of clinical success; drug of choice for infertility; but troublesome side effects can occur

-cabergoline: most tolerable preparation with less side effects; biweekly dosing and expensive

Front 42

What can high doses of cabergolien and pergolide (in PD) be associated with?

Back 42

valvular heart disease: due to activation of valvular serotonin receptors

Front 43

what is pituitary gigantism?

Back 43

excessive linear growth due to excess growth hormone secretion in infants, children, and adolescents who have open epiphiseal growth plates; often accompanied by obesity, acral enlargement, etc

Front 44

what causes pituitary gigantism?

Back 44

growth hormone secreting tumors, GhRH secreting tumors, or somatostatin dysregulation

Front 45

What percent of people with acromegaly have macroadenoma and when do symptoms occur before diagnosis?

Back 45

-70% and 10-12 years

Front 46

What are three groupings of systemic abnormalities with acromegaly?

Back 46

-visceromegaly(liver, spleen, thyroid, salivary glands, kidney, prostate)

-pulmonary (obstructive sleep apnea and narcolepsy)

-mineral and electrolyte abnormaliteis: low renin and increased aldosterone; hypercalciuria, and hypervitimonisis 25D

Front 47

what are somatic symptoms of acromegaly?

Back 47

-acrla enlargement
-frontal bossing
-jaw malocclusion
-arthralgias and arthritis; carpal tunnel syndrome
-proximal myopathy and acroparasthesisas

Front 48

acromegaly systemic abnormalities: skin and GI systems:

Back 48

hyperhydrosis; oily skin; skin tags, colonic polyps

Front 49

cardiovascular systemic abnormalities of acromegaly:

Back 49

cardiomyopathy, ventricular hypertrophy, hypertension, congestive failure

Front 50

acromegaly: reproductive abnormalities:

Back 50

menstraul, galactorreha, hirsuitism, decreased libido and erectile dysfunction

Front 51

acromegaly: carbohydrate and lipid abnormalities:

Back 51

insulin resistance and impaired glucose tolerance ;diabetes mellitus, hypertriglyceridemia

Front 52

acromegalic hands:

Back 52

distal tufting of the terminal phalanges

Front 53

acromegally diagnostic logarithm:

Back 53

increased IGF1--> test oral glucose tolerance: if normal than no diagnosis
-if nadir s/p 75 gm GLU hgh > 1 ug/dl then acromegaly suspicion confirmed

Front 54

What are 5 uses of somatostatin and somatostatin analogues?

Back 54

-suppress growth hormone secretion and tumor growth in acromegaly
-suppress hepatic synthesis of IGF1
-suppress TSH secretion in TSH secreting tumors
-suppress GI hormone secretion in Gi endocrine tumors (VIP, carcinoid, glucagonoma)
-20% of patients develop gall stones or "sludge" with long term use

Front 55

What are three somatostatin analogues?

Back 55

1.) octreotide: short acting somatostatin analogue interacts with SST1 and SST5 which are expressed in 90% of growth hormone secreting tumors!
2.) octreotide LAR: long acting release preparation given monthly
3.) lanreotide gel: now available in US similar to octreotide activity

Front 56

somatostatin and analogues:

Back 56

identification as inhibitor of growth hormone; widespread transmitter activity; cleaved from prohormone 28 AA to 14 AA forms

--> 5 diff somatostatin receptors (SST1-5): analogues have selective activity due to diff receptor affinity and activity

Front 57

SST analogues: potent effects limited to what type of SST?

Back 57

sst2
-pasireotide is a newly developed SST analogue that has activity at SST 1,2,3,and 5: emerging as helpful in tumors resistant to surgery and pharmacologic intervention (especually in HGH and ACTH tumors expressing SST5)
-clinical use: limited by effects on SST 5: impairs insulin release causing hyperglycemia
-Somatoprim: a specific SST3 analogue also in development and is not likely a cause of hyperglycemia

Front 58

What are features of GH receptor antagonists?

Back 58

-receptor dimerization leads to cascade of phosphorylase activity leading to IGF1 secretion; gh interacts with binding sites to promote phosphorylation and antagonists prevent binding

Front 59

What are three types of treatment for the three types of hypothalamic tumors?

Back 59

1.) microadenomas < 10 mm may be completely removed with transphenoidal surgery
2.) macroadenomas > 10 mm with suprasellar extension surgical cure is less likely
3.) hypothalamic tumors (Craniopharyngioma) TSS or transfrontal approach may be necessary for complete removal

Front 60

describe a transphenoidal hypophysectomy:

Back 60

a direct or endoscopic approach from below or throw the sphenoidal sinus

Front 61

describe a transfrontal open craniotomy:

Back 61

major intracranial surgery anteriorly through the frontal area of the skull

Front 62

What are two types of radiation therapy and two types of pharmacologic therapy for pituitary tumors?

Back 62

radiation: conventional and gamma knife

pharm: somatostatin analogues for acromegaly and TSH secreting tumors

-dopaminergic agonists for prolactinoma and acromegaly

Front 63

What are two hallmarks of hypopituitarism?

Back 63

growth retardation in children and abnormal menses in women

Front 64

What are the genetic causes of hypopituitarism: (rare)?

Back 64

-structural defect (pituitary aplasia)
-isolated defect in hypophysiotropic hormone or pituitary hormone (GnRH in kallman's syndrome; anosmia and hypogonadism)
-isolated defect in hormone receptors: CRH
-isolated hormone mutation (etc).

Front 65

What genetic mutations in TF are involved in organogenesis and differentiation?

Back 65

HEXS1: GH, PRL< TSH, LH, FSH, ACTH: septo-optic dysplasia
PROP-1: (most common): Gh, PRL, TSH, Lh, FSH +/- ACTH
PIT1 (pou1F1): Gh, PRL, TSH)
-T-pit: ACTH (red hair and obesity)

Front 66

list examples of intrapituitary tumor, extrapituitary tumor, and vascular pituitary causes of Hypopituitarism:

Back 66

1.) intrapituitary tumor
2.) extrapituitary (craniopharyngioma; rathke's cleft cyst)
3.) vascular: sheehan's syndrome: pitutiary infarction at delivery ;pituitary apoplexy (sudden pituitary hemorrhage) and ischemic infarction (coronary bypass)

Front 67

what are features of growth hormone and aging?

Back 67

-aging blunts amplitude and decreases frequency of GH secretion
-IGF-1 levels: 20-70% lower in healthy aging adults than young controls
-GH treatmetn: no impressive additive benefits to exercise on muscle strength, bone density, etc.
-side effects: carpal tunnel Sx, fluid retention, hyperglycemia occur
-theoretical concern Re Gi and other malignancies

Front 68

syndrome of inappropriate anti-diuretic hormone release:

Back 68

-ADH leads to inappropriate volume expansion due to water retention
-volume expansion overrides sodium handling with inappropriate urinary sodium loss
-clinical hallmark is hyponatremia (< 135 meq) with evidence of relative water excess

Front 69

what are clinical features of SIADH:

Back 69

-euvolemia (no edema, no signs of dehydration)
-decreased serum sodium and osmolality with apparent relative increase water to solute
-inappropriate: less than maximal urine dilution despite dilutional hypo-osmolality
-inappropriate urine sodium loss despite low serum sodium

Front 70

treatment of SIADH:

Back 70

-restrict fluid intake
-gentle administration of hypertonic fluids to reverse symptoms
-drugs which impair renal responses to ADH: demeclocline and lithium and vasopressin antagonists