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Jimmy Santana, MBA, P.A.-CJimmy Santana, MBA, P.A.-C

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Pituitary and Hypothalamic Pituitary and Hypothalamic DisordersDisorders

Hypothalamic DysfunctionHypothalamic Dysfunction Craniopharyngioma:Craniopharyngioma: most frequent cause of most frequent cause of

hypothalamic dysfunction in children and young adultshypothalamic dysfunction in children and young adults Primary central nervous system tumors, Primary central nervous system tumors,

pinealomas, dermoid and epidermoid tumors seen pinealomas, dermoid and epidermoid tumors seen in adulthoodin adulthood

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ENDOCRINOLOGYENDOCRINOLOGY Hypothalamic dysfunctionHypothalamic dysfunction

S&S: visual loss, headache and vomiting ( due to S&S: visual loss, headache and vomiting ( due to raised intracranial pressure), hypopituitarism raised intracranial pressure), hypopituitarism including growth failure and diabetes insipidus including growth failure and diabetes insipidus (DI).(DI).

Hypothalamic disturbances can cause disorders of Hypothalamic disturbances can cause disorders of thirst, appetite, temperature regulation, behavior thirst, appetite, temperature regulation, behavior and consciousness and consciousness

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ENDOCRINOLOGYENDOCRINOLOGY Craniopharyngioma is tx’ed primarily Craniopharyngioma is tx’ed primarily

w/surgical resection and then radiotherapyw/surgical resection and then radiotherapy Biopsy of other tumors required as germinoma Biopsy of other tumors required as germinoma

is very radiosensitiveis very radiosensitive HypopituitarismHypopituitarism

results from decreased secretion of pituitary results from decreased secretion of pituitary hormone(s)hormone(s)

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ENDOCRINOLOGYENDOCRINOLOGY Hypopituitarism can occur from:Hypopituitarism can occur from:

pituitary gland dysfunction due to deficiency of pituitary gland dysfunction due to deficiency of hypothalamic stimulatory/inhibitory factorshypothalamic stimulatory/inhibitory factors

anterior pituitary gland destructionanterior pituitary gland destruction congenital or acquired lesionscongenital or acquired lesions

lesions may cause single or multiple hormonal losseslesions may cause single or multiple hormonal losses

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ENDOCRINOLOGYENDOCRINOLOGY GH DeficiencyGH Deficiency

manifests in infancy and childhood as growth manifests in infancy and childhood as growth retardation, short stature and fasting hypoglycemiaretardation, short stature and fasting hypoglycemia

in adults, may present as increased abdominal in adults, may present as increased abdominal adiposity, reduced strength and exercise capacity, adiposity, reduced strength and exercise capacity, cold intolerance, and impaired psychosocial well-cold intolerance, and impaired psychosocial well-beingbeing

usually presents w/ other symptoms of usually presents w/ other symptoms of panhypopituitarismpanhypopituitarism

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ENDOCRINOLOGYENDOCRINOLOGY GH reserve evalGH reserve eval

provocative test are used to indirectly stimulate provocative test are used to indirectly stimulate somatotrophsomatotroph

required in assessing children w/short staturerequired in assessing children w/short stature GH basal levels are frequently low in nl individualsGH basal levels are frequently low in nl individuals

may also help in work-up of adults w/suspected may also help in work-up of adults w/suspected hypopituitarismhypopituitarism

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ENDOCRINOLOGYENDOCRINOLOGY GH reserveGH reserve

Clonidine and propranolol given orally Clonidine and propranolol given orally Arginine infusion, L-dopa (precursor of Arginine infusion, L-dopa (precursor of

dopamine), norepinephrine and insulin are dopamine), norepinephrine and insulin are used to stimulate secretion from pituitary used to stimulate secretion from pituitary somatotrophsomatotroph

Insulin-induced hypoglycemia is the most Insulin-induced hypoglycemia is the most reliable stimulus of GH hyper-secretionreliable stimulus of GH hyper-secretion

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ENDOCRINOLOGYENDOCRINOLOGY In elderly or pts w/CNS disordersIn elderly or pts w/CNS disorders

avoid insulin-induced hypoglycemiaavoid insulin-induced hypoglycemia Multiple tests used to dx GH deficiencyMultiple tests used to dx GH deficiency

approx 90% respond to one testapprox 90% respond to one test Insulin-like growth factors and Binding Insulin-like growth factors and Binding

proteins(IGF-BP) produced by liverproteins(IGF-BP) produced by liver low levels of IGF-BP3 can be used to to screen for GH low levels of IGF-BP3 can be used to to screen for GH

deficiency, which is regulated by GH deficiency, which is regulated by GH

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ENDOCRINOLOGYENDOCRINOLOGY Hypothalamic dysfunctionHypothalamic dysfunction

a single dose of GHRH can be used to stimulate a single dose of GHRH can be used to stimulate GH secretionGH secretion

GH deficiency from hypopituitarism does not respond GH deficiency from hypopituitarism does not respond to GHRH dose stimulationto GHRH dose stimulation

TSH deficiencyTSH deficiency caused by thyroid gland hypo-function and caused by thyroid gland hypo-function and

involutioninvolution

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ENDOCRINOLOGYENDOCRINOLOGY TSH deficiencyTSH deficiency

S&S: Hypothyroidism : lethargy, constipation, S&S: Hypothyroidism : lethargy, constipation, cold intolerance, cold-stimulate, bradycardia, cold intolerance, cold-stimulate, bradycardia, weight gain, poor appetite, dry skin, delayed weight gain, poor appetite, dry skin, delayed reflexesreflexes

secondary hypothyroidism can be differentiated secondary hypothyroidism can be differentiated from primary hypothyroidism by presence of low from primary hypothyroidism by presence of low circulating TSH in presence of low thyroid circulating TSH in presence of low thyroid hormone levelshormone levels

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ENDOCRINOLOGYENDOCRINOLOGY TSH evalTSH eval

Thyroid function tests (free thyroxine {FT4}, free Thyroid function tests (free thyroxine {FT4}, free tri-iodothyronine {FT3}, or free thyroxine index tri-iodothyronine {FT3}, or free thyroxine index {FT1}){FT1})

TSH measurement needed in presence of low thyroid TSH measurement needed in presence of low thyroid function test to differentiate primary gland failure function test to differentiate primary gland failure ( elevated TSH) from hypothyroidism from ( elevated TSH) from hypothyroidism from hypothalamic/pituitary gland failure (low or hypothalamic/pituitary gland failure (low or inappropriately normal TSH)inappropriately normal TSH)

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ENDOCRINOLOGYENDOCRINOLOGY Gonatropin deficiencyGonatropin deficiency

failure to enter puberty is due to central failure to enter puberty is due to central hypogonadism during childhoodhypogonadism during childhood

females have delayed breast development, scant pubic females have delayed breast development, scant pubic and axillary hair, and primary amenorrheaand axillary hair, and primary amenorrhea

boys have sparse body hair and phalus and testes remain boys have sparse body hair and phalus and testes remain smallsmall

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ENDOCRINOLOGYENDOCRINOLOGY In gonadotropin deficiency, growth continues In gonadotropin deficiency, growth continues

(GH is intact), epiphyses on long bones fail to (GH is intact), epiphyses on long bones fail to fuse due to absence of sex steroids which is fuse due to absence of sex steroids which is needed for fusing of epiphyseal growth platesneeded for fusing of epiphyseal growth plates adolescents become tall with eunuchoid adolescents become tall with eunuchoid

proportions ( upper-to-lower segment ration <1) proportions ( upper-to-lower segment ration <1)

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ENDOCRINOLOGYENDOCRINOLOGY Gonadotropin deficiencyGonadotropin deficiency

in adult women; hypogonadism presents as loss of in adult women; hypogonadism presents as loss of axillary and pubic hair, breast atrophy and axillary and pubic hair, breast atrophy and secondary amenorrheasecondary amenorrhea

in adult males; they have testicular atrophy, in adult males; they have testicular atrophy, decreased libido, impotence and loss of body hairdecreased libido, impotence and loss of body hair

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ENDOCRINOLOGYENDOCRINOLOGY Hypothalamic-Pituitary-Gonadal AxisHypothalamic-Pituitary-Gonadal Axis

best dx’ed w/concurrent measurement of serum best dx’ed w/concurrent measurement of serum gonadotropins and gonadal steroid concentrationsgonadotropins and gonadal steroid concentrations

in amenorrheic women serum LH, FSH, estradiol, in amenorrheic women serum LH, FSH, estradiol, prolactin and Human chorionic gonadatropin prolactin and Human chorionic gonadatropin (Hcg) must be measured(Hcg) must be measured

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ENDOCRINOLOGYENDOCRINOLOGY Primary ovarian failurePrimary ovarian failure

elevated FSH and LH, nl prolactin levelselevated FSH and LH, nl prolactin levels HyperprolactinemiaHyperprolactinemia

elevated prolactin lvls, normal follicular phase LH, elevated prolactin lvls, normal follicular phase LH, FSH, and estradiol lvlsFSH, and estradiol lvls

lvs >200ng/dl of PRL secreting adenomaslvs >200ng/dl of PRL secreting adenomas PregnancyPregnancy

(+) Hcg, nl to high prolactin lvl, nl to high LH, high (+) Hcg, nl to high prolactin lvl, nl to high LH, high estradioestradio

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ENDOCRINOLOGYENDOCRINOLOGY Low to nl FSH/LH lvls w/low testosterone Low to nl FSH/LH lvls w/low testosterone

(males) and estradiol (females) confirms (males) and estradiol (females) confirms Gonadotropin deficiencyGonadotropin deficiency

Low gonadal steroids w/elevated Low gonadal steroids w/elevated gonadotropins suggest primary gonadal failuregonadotropins suggest primary gonadal failure

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ENDOCRINOLOGYENDOCRINOLOGY ACTH deficiencyACTH deficiency

results in adrenocorticol insufficiency results in adrenocorticol insufficiency w/decreased cortisol and androgen secretionw/decreased cortisol and androgen secretion

results in adrenal failureresults in adrenal failure S&S: lethargy, weakness, nausea, vomiting, S&S: lethargy, weakness, nausea, vomiting,

dehydration, orthostatic hypotension and if not tx’ed dehydration, orthostatic hypotension and if not tx’ed comacoma

if not recognized and tx’ed may lead to DEATHif not recognized and tx’ed may lead to DEATH

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ENDOCRINOLOGYENDOCRINOLOGY ACTH evalACTH eval

Basal lvls: unreliable due to short plasma half-life Basal lvls: unreliable due to short plasma half-life and pulsatile secretionand pulsatile secretion

ACTH regulates cortisol secretionACTH regulates cortisol secretion plasma cortisol lvls reflect hypothalamic-pituitary-plasma cortisol lvls reflect hypothalamic-pituitary-

adrenal functionadrenal function an 8am lvl > 10micro/dl will r/o adrenal insufficiency, an 8am lvl > 10micro/dl will r/o adrenal insufficiency,

but does not assess adrenal reservebut does not assess adrenal reserve

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ENDOCRINOLOGYENDOCRINOLOGY ACTH evalACTH eval

adrenal insufficiency from a primary adrenal adrenal insufficiency from a primary adrenal disorder nl to high ACTH plasma lvlsdisorder nl to high ACTH plasma lvls

adrenal insufficiency due to hypothalamic-adrenal insufficiency due to hypothalamic-pituitary hypo-function will show low to absent pituitary hypo-function will show low to absent ACTH lvlsACTH lvls

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ENDOCRINOLOGYENDOCRINOLOGY ACTH reserve evalACTH reserve eval

adrenal atrophy results from prolonged ACTH adrenal atrophy results from prolonged ACTH deficiency : adrenal cortisol reserve can be deficiency : adrenal cortisol reserve can be measured indirectly by testing pituitary ACTHmeasured indirectly by testing pituitary ACTH

inadequate response implies primary adrenal failure or inadequate response implies primary adrenal failure or impaired pituitary ACTH secretionimpaired pituitary ACTH secretion

provocative testing is performed under stressprovocative testing is performed under stress potentially hazardous if adrenal function is potentially hazardous if adrenal function is

compromisedcompromised

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ENDOCRINOLOGYENDOCRINOLOGY ADH (Vasopressin) deficiencyADH (Vasopressin) deficiency

ADH deficiency results in a lg vol of urine which ADH deficiency results in a lg vol of urine which is very diluteis very dilute

occurs w/posterior pituitary dysfunctionoccurs w/posterior pituitary dysfunction leads to Diabetes Insipidus (DI), polyuria, polydypsia leads to Diabetes Insipidus (DI), polyuria, polydypsia

and nocturiaand nocturia

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ENDOCRINOLOGYENDOCRINOLOGY DIDI

Central (neurogenic) origin: failure of posterior Central (neurogenic) origin: failure of posterior pituitary to secrete adequate amts of ADHpituitary to secrete adequate amts of ADH

Nephrogenic origin: failure of kidney to respond Nephrogenic origin: failure of kidney to respond to circulating ADHto circulating ADH

regardless of cause, pts secret lg volumes of dilute regardless of cause, pts secret lg volumes of dilute urine causing cellular and extra-cellular urine causing cellular and extra-cellular dehydration resulting in excess thirstdehydration resulting in excess thirst

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ENDOCRINOLOGYENDOCRINOLOGY DI needs to be differentiated from:DI needs to be differentiated from:

Primary polydypsia a compulsive psychoneurotic Primary polydypsia a compulsive psychoneurotic disorder appearing as a thirst disorder. Pt drinks > disorder appearing as a thirst disorder. Pt drinks > 5L of water a day5L of water a day

results in decreased ADH secretion and water causes results in decreased ADH secretion and water causes subsequent diuresissubsequent diuresis

plasma and urine are dilute as opposed to DI where plasma and urine are dilute as opposed to DI where urine osmolarity is less than plasma osmolarity due to urine osmolarity is less than plasma osmolarity due to inappropriate water diuresis inappropriate water diuresis

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ENDOCRINOLOGYENDOCRINOLOGY Primary test for cause of polyuriaPrimary test for cause of polyuria

water deprivation for 12- 18hrswater deprivation for 12- 18hrs body wght, BP,urine vol, urine specific gravity, body wght, BP,urine vol, urine specific gravity,

plasma and osmolarity measured q 2hrsplasma and osmolarity measured q 2hrs nl response is decreased urine output, increased urine nl response is decreased urine output, increased urine

concentration greater than plasmaconcentration greater than plasma pts w/DI maintain high dilute urine outputpts w/DI maintain high dilute urine output pts w/primary polydypsia have urine omsolarity greater pts w/primary polydypsia have urine omsolarity greater

than plasma than plasma

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ENDOCRINOLOGYENDOCRINOLOGY DIDI

water deprivation cont until plasma lvl plateaus, water deprivation cont until plasma lvl plateaus, then AVP is given and urine osmolarity is checked then AVP is given and urine osmolarity is checked in 1hrin 1hr

pts w/ complete central DI; urine osmolarity increases pts w/ complete central DI; urine osmolarity increases to about plasma osmolarityto about plasma osmolarity

pts w/ nephrogenic DI; osmolarity of urine increases pts w/ nephrogenic DI; osmolarity of urine increases less than 50%less than 50%

pts w/primary poldypsia; osmolarity increases <10% pts w/primary poldypsia; osmolarity increases <10%

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ENDOCRINOLOGYENDOCRINOLOGY Central DI txCentral DI tx

Desmopressin acetate (DDAVP) intranasal or Desmopressin acetate (DDAVP) intranasal or orallyorally

serum osmolarity and sodium is monitoredserum osmolarity and sodium is monitored Nephrogenic DI txNephrogenic DI tx

seek underlying causeseek underlying cause maintain a state of mild sodium depletion maintain a state of mild sodium depletion

w/reduction in solute load on kidney by giving w/reduction in solute load on kidney by giving diuretics and salt restrictiondiuretics and salt restriction

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ENDOCRINOLOGYENDOCRINOLOGY Syndrome of Inappropriate secretion of Syndrome of Inappropriate secretion of

Antidiuretic Hormone (SIADH)Antidiuretic Hormone (SIADH) plasma ADH concentrations inappropriately high plasma ADH concentrations inappropriately high

for plasma osmolarityfor plasma osmolarity leads to water retention and hyponatremia w/ decrease leads to water retention and hyponatremia w/ decrease

plasma osmolarityplasma osmolarity dx can only be made in absence of hyper-volumemia dx can only be made in absence of hyper-volumemia

(nephrotic syndrome, cardiac failure, cirrhosis) and w/ (nephrotic syndrome, cardiac failure, cirrhosis) and w/ nl thyroid, adrenal and renal functionnl thyroid, adrenal and renal function

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ENDOCRINOLOGYENDOCRINOLOGY SIADHSIADH

S&S: depends on degree of hyponatremia and rate S&S: depends on degree of hyponatremia and rate of fall of plasma osmolarityof fall of plasma osmolarity

HA, anorexia, vomiting and confusion w/ sodium lvls HA, anorexia, vomiting and confusion w/ sodium lvls between 115 and 120mEq/lbetween 115 and 120mEq/l

w/ lvs <110mEq/l; disorientation, stupor, coma, w/ lvs <110mEq/l; disorientation, stupor, coma, seizures, paralysis, and focal neurologic findingsseizures, paralysis, and focal neurologic findings

several malignant and benign conditions are several malignant and benign conditions are associated w/SIADHassociated w/SIADH

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ENDOCRINOLOGYENDOCRINOLOGY Disorders associated w/SIADHDisorders associated w/SIADH

Pulmonary: malignant- Oat cell carcinomaPulmonary: malignant- Oat cell carcinomabenign- TB, pneumonia, abscessbenign- TB, pneumonia, abscess CNS: meningitis, brain abscess, hd traumaCNS: meningitis, brain abscess, hd trauma Adverse drug effects: Clofibrate, Chlorpropamide, Adverse drug effects: Clofibrate, Chlorpropamide,

Cyclophosmamide, Phenothiazine, CarbamazapineCyclophosmamide, Phenothiazine, Carbamazapine Tumors (ectopic production of ADH): lymphoma, Tumors (ectopic production of ADH): lymphoma,

Sarcoma, Carcinoma of pancreas or duodenumSarcoma, Carcinoma of pancreas or duodenum

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