Transcript ENDOCRINOLOGY

ENDOCRINOLOGY
BOARD REVIEW
Presented by Med/Peds PGY III Class
ENDOCRINOLOGY
Disorders of the
Hypothalamic – Pituitary
Axis
K. Dionne Posey, MD, MPH
ENDOCRINOLOGY
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Pituitary Disorders
Thyroid Disorders
Adrenal Disorders
Gonadal Disorders
Calcium Disorders
Lipid Disorders
Endocrine diseases
Hormone excess
Hormone deficiency
Hormone resistance
Hypothalamic–Pituitary
Axis
Pituitary Gland
• Located within the sella tursica
• Contiguous to vascular and neurologic
structures
– Cavernous sinuses
– Cranial nerves
– Optic chiasm
• Hypothalamic neural cells synthesize specific
releasing and inhibiting hormones
– Secreted directly into the portal vessels of the
pituitary stalk
• Blood supply derived from the superior and
inferior hypophyseal arteries
Pituitary Gland
• Anterior pituitary gland
– Secrete various trophic hormones
– Disease in this region may result in syndromes of
hormone excess or deficiency
• Posterior pituitary gland
– More of a terminus of axons of neurons in the
supraoptic and paraventricular nuclei of the
hypothalamus
– Storehouse for the hormones
– The main consequence of disease in this area is
disordered water homeostasis
Anterior Pituitary Gland
• Anterior Pituitary
“Master gland”
– Major blood source: hypothalamic-pituitary portal
plexus
• Allows transmission of hypothalamic peptide pulses
without significant systemic dilution
• Consequently, pituitary cells are exposed to sharp spikes
of releasing factors and in turn release their hormones as
discrete pulses
– Production of six major hormones:
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Prolactin (PRL)
Growth hormone (GH)
Adrenocorticotropin hormone (ACTH)
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH)
Thyroid-stimulating hormone (TSH)
Anterior Pituitary Gland
• Anterior Pituitary
“Master gland”
– Secreted in a pulsatile manner
– Elicits specific responses in peripheral target
tissues
– Feedback control at the level of the
hypothalamus and pituitary to modulate pituitary
function exerted by the hormonal products of the
peripheral target glands
– Tumors cause characteristic hormone excess
syndromes
– Hormone deficiency
• may be inherited or acquired
Hypopituitarism
Gonadotropin Deficiency
Women
• Oligomenorrhea or
amenorrhea
• Loss of libido
• Vaginal dryness or
dyspareunia
• Loss of secondary
sex characteristics
(estrogen deficiency)
Men
• Loss of libido
• Erectile dysfunction
• Infertility
• Loss of secondary
sex characteristics
(testosterone
deficiency)
• Atrophy of the testes
• Gynecomastia
(testosterone
deficiency)
ACTH Deficiency
• Results in hypocortisolism
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Malaise
Anorexia
Weight-loss
Gastrointestinal disturbances
Hyponatremia
• Pale complexion
– Unable to tan or maintain a tan
• No features of mineralocorticoid deficiency
– Aldosterone secretion unaffected
TSH Deficiency
• Hypothyroidism
• Atrophic thyroid gland
Prolactin Deficiency
• Inability to lactate postpartum
• Often 1st manifestation of Sheehan
syndrome
Growth Hormone
Deficiency
• Adults
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Often asymptomatic
May complain of
Fatigue
Degrees exercise tolerance
Abdominal obesity
Loss of muscle mass
• Children
– GH Deficiency
– Constitutional growth delay
Hypopituitarism
Etiology
• Anterior pituitary diseases
– Deficiency one or more or all anterior pituitary
hormones
• Common causes:
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Primary pituitary disease
Hypothalamic disease
Interruption of the pituitary stalk
Extrasellar disorders
Hypopituitarism
– Primary pituitary disease
• Tumors
• Pituitary surgery
• Radiation treatment
– Hypothalamic disease
• Functional suppression of
axis
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Exogenous steroid use
Extreme weight loss
Exercise
Systemic Illness
– Interruption of the
pituitary stalk
– Extrasellar disorders
• Craniopharyngioma
• Rathke pouch
Hypopituitarism
Hypopituitarism
• Developmental and
genetic causes
– Dysplasia
• Septo-Optic dysplasia
– Developmental
hypothalamic
dysfunction
• Kallman Syndrome
• Laurence-MoonBardet-Biedl
Syndrome
• Frohlich Syndrome
(Adipose Genital
Dystrophy)
• Acquired causes:
– Infiltrative disorders
– Cranial irradiation
– Lymphocytic
hypophysitis
– Pituitary Apoplexy
– Empty Sella syndrome
Hypopituitarism: Developmental and
Genetic causes
• Septo-Optic dysplasia
• Kallman Syndrome
• Laurence-Moon-Bardet-Biedl Syndrome
• Frohlich Syndrome (Adipose Genital
Dystrophy)
Hypopituitarism: Genetic
– Septo-Optic dysplasia
– Hypothalamic dysfunction and hypopituitarism
» may result from dysgenesis of the septum pellucidum
or corpus callosum
– Affected children have mutations in the HESX1 gene
» involved in early development of the ventral
prosencephalon
– These children exhibit variable combinations of:
» cleft palate
» syndactyly
» ear deformities
» hypertelorism
» optic atrophy
» micropenis
» anosmia
– Pituitary dysfunction
» Diabetes insipidus
» GH deficiency and short stature
» Occasionally TSH deficiency
Hypopituitarism: Developmental
• Kallman Syndrome
• Defective hypothalamic gonadotropin-releasing hormone
(GnRH) synthesis
• Associated with anosmia or hyposmia due to olfactory
bulb agenesis or hypoplasia
• May also be associated with: color blindness, optic
atrophy, nerve deafness, cleft palate, renal abnormalities,
cryptorchidism, and neurologic abnormalities such as
mirror movements
• GnRH deficiency prevents progression through
puberty
• characterized by
– low LH and FSH levels
– low concentrations of sex steroids
Hypopituitarism: Developmental
• Kallman Syndrome
• Males patients
– Delayed puberty and hypogonadism, including micropenis
» result of low testosterone levels during infancy
– Long-term treatment:
» human chorionic gonadotropin (hCG) or testosterone
• Female patients
– Primary amenorrhea and failure of secondary sexual
development
– Long-term treatment:
» cyclic estrogen and progestin
• Diagnosis of exclusion
• Repetitive GnRH administration restores normal pituitary
• Fertility may also be restored by the administration of
gonadotropins or by using a portable infusion pump to
deliver subcutaneous, pulsatile GnRH
Hypopituitarism: Developmental
• Laurence-Moon-Bardet-Biedl Syndrome
• Rare autosomal recessive disorder
• Characterized by mental retardation; obesity;
and hexadactyly, brachydactyly, or syndactyly
• Central diabetes insipidus may or may not be
associated
• GnRH deficiency occurs in 75% of males and
half of affected females
• Retinal degeneration begins in early childhood
– most patients are blind by age 30
Hypopituitarism: Developmental
• Frohlich Syndrome (Adipose Genital
Dystrophy)
• A broad spectrum of hypothalamic lesions
– hyperphagia, obesity, and central hypogonadism
• Decreased GnRH production in these patients
results in
– attenuated pituitary FSH and LH synthesis and
release
• Deficiencies of leptin, or its receptor, cause
these clinical features
Hypopituitarism
• Acquired causes:
– Infiltrative disorders
– Cranial irradiation
– Lymphocytic hypophysitis
– Pituitary Apoplexy
– Empty Sella syndrome
Hypopituitarism: Acquired
• Lymphocytic Hypophysitis
– Etiology
• Presumed to be autoimmune
– Clinical Presentation
• Women, during postpartum period
• Mass effect (sellar mass)
• Deficiency of one or more anterior pituitary hormones
– ACTH deficiency is the most common
– Diagnosis
• MRI - may be indistinguishable from pituitary adenoma
– Treatment
• Corticosteroids – often not effective
• Hormone replacement
Hypopituitarism: Acquired
• Pituitary Apoplexy
– Hemorrhagic infarction of a pituitary
adenoma/tumor
– Considered a neurosurgical emergency
– Presentation:
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Variable onset of severe headache
Nausea and vomiting
Meningismus
Vertigo
+/ - Visual defects
+/ - Altered consciousness
– Symptoms may occur immediately or may develop
over 1-2 days
Hypopituitarism: Acquired
• Pituitary Apoplexy
– Risk factors:
• Diabetes
• Radiation treatment
• Warfarin use
– Usually resolve completely
– Transient or permanent hypopituitarism is possible
• undiagnosed acute adrenal insufficiency
– Diagnose with CT/MRI
– Differentiate from leaking aneurysm
– Treatment:
• Surgical - Transsphenoid decompression
– Visual defects and altered consciousness
– Medical therapy – if symptoms are mild
• Corticosteroids
Quick Quiz!!!
• When should you suspect pituitary
apoplexy?
MedStudy 2005 - Endocrine
Answer
• Suspect in patient presenting with
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Variable onset of severe headache
Nausea and vomiting
Meningismus
Vertigo
+/ - Visual defects
+/ - Altered consciousness
Hypopituitarism: Acquired
• Empty Sella Syndrome
– Often an incidental MRI finding
– Usually have normal pituitary function
• Implying that the surrounding rim of pituitary tissue is fully
functional
– Hypopituitarism may develop insidiously
– Pituitary masses may undergo clinically silent
infarction with development of a partial or totally
empty sella by cerebrospinal fluid (CSF) filling the
dural herniation.
– Rarely, functional pituitary adenomas may arise
within the rim of pituitary tissue, and these are not
always visible on MRI
Hypopituitarism
Clinical Presentation
• Can present with features of deficiency
of one or more anterior pituitary
hormones
• Clinical presentation depends on:
– Age at onset
– Hormone effected, extent
– Speed of onset
– Duration of the deficiency
Hypopituitarism
Diagnosis
• Biochemical diagnosis of pituitary
insufficiency
– Demonstrating low levels of trophic
hormones in the setting of low target
hormone levels
• Provocative tests may be required to
assess pituitary reserve
Hypopituitarism
Treatment
• Hormone replacement therapy
– usually free of complications
• Treatment regimens that mimic
physiologic hormone production
– allow for maintenance of satisfactory
clinical homeostasis
Hormone Replacement
Trophic Hormone Deficit
Hormone Replacement
ACTH
Hydrocortisone (10-20 mg A.M.; 10 mg P.M.)
Cortisone acetate (25 mg A.M.; 12.5 mg P.M.)
Prednisone (5 mg A.M.; 2.5 mg P.M.)
TSH
L-Thyroxine (0.075-0.15 mg daily)
FSH/LH
Males
Testosterone enanthate (200 mg IM every 2 wks)
Testosterone skin patch (5 mg/d)
Females
Conjugated estrogen (0.65-1.25 mg qd for 25days)
Progesterone (5-10 mg qd) on days 16-25
Estradiol skin patch (0.5 mg, every other day)
For fertility: Menopausal gonadotropins, human
chorionic gonadotropins
GH
Adults: Somatotropin (0.3-1.0 mg SC qd)
Children: Somatotropin [0.02-0.05 (mg/kg per day)]
Vasopressin
Intranasal desmopressin (5-20 ug twice daily)
Oral 300-600 ug qd
Take home points:
• Remember that the cause may be functional
– Treatment should be aimed at the underlying cause
• Hypopituitarism may present
– Acutely with cortisol deficiency
– After withdrawal of prolonged glucocorticoid therapy
that has caused suppression of the HPA axis.
– Post surgical procedure
– Post trauma
• Hemorrhage
• Exacerbation of cortisol deficiency in a patient
with unrecognized ACTH deficiency
– Medical/surgical illness
– Thyroid hormone replacement therapy
Pituitary Tumors
Pituitary Tumors
• Microadenoma < 1 cm
• Macroadenoma > 1 cm
• Is the tumor causing local mass effect?
• Is hypopituitarism present?
• Is there evidence of hormone excess?
• Clinical presentation:
– Mass effect
• Superior extension
– May compromise optic pathways – leading to impaired visual
acuity and visual field defects
– May produce hypothalamic syndrome – disturbed thirst, satiety,
sleep, and temperature regulation
• Lateral extension
– May compress cranial nerves III, IV, V, and VI – leaning to diplopia
• Inferior extension
– May lead to cerebrospinal fluid rhinorrhea
Pituitary Tumors
• Diagnosis
– Check levels of all hormones produced
– Check levels of target organ products
• Treatment
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Surgical excision, radiation, or medical therapy
Generally, first-line treatment surgical excision
Drug therapy available for some functional tumors
Simple observation
• Option if the tumor is small, does not have local mass
effect, and is nonfunctional
• Not associated with clinical features that affect quality of
life
Craniopharyngioma
– Derived from Rathke's pouch.
– Arise near the pituitary stalk
• extension into the suprasellar cistern common
– These tumors are often large, cystic, and locally
invasive
– Many are partially calcified
• characteristic appearance on skull x-ray and CT images
– Majority of patients present before 20yr
• usually with signs of increased intracranial pressure,
including headache, vomiting, papilledema, and
hydrocephalus
Craniopharyngioma
• Associated symptoms include:
– visual field abnormalities, personality changes
and cognitive deterioration, cranial nerve damage,
sleep difficulties, and weight gain.
• Children
– growth failure associated with either
hypothyroidism or growth hormone deficiency is
the most common presentation
• Adults
– sexual dysfunction is the most common problem
– erectile dysfunction
– amenorrhea
Craniopharyngioma
• Anterior pituitary dysfunction and diabetes
insipidus are common
• Treatment
– Transcranial or transsphenoidal surgical resection
• followed by postoperative radiation of residual tumor
• This approach can result in long-term survival and
ultimate cure
• most patients require lifelong pituitary hormone
replacement.
• If the pituitary stalk is uninvolved and can be
preserved at the time of surgery
– Incidence of subsequent anterior pituitary
dysfunction is significantly diminished.
Quick Quiz!!!
• How does prolactin differ from LH/FSH
in regard to hypothalamic control?
Answer
• Tonic hypothalamic inhibition by
Dopamine
Prolactinoma
• Most common functional pituitary tumor
• Usually a microadenoma
• Can be a space occupying macroadenoma –
often with visual field defects
• Although many women with
hyperprolactinemia will have galactorrhea
and/ or amenorrhea
– The absence these the two signs do not excluded
the diagnosis
• GnRH release is decreased in direct
response to elevated prolactin, leading to
decreased production of LH and FSH
Prolactinoma
• Women
– Amenorrhea – this symptom causes
women to present earlier
– Hirsutism
• Men
– Impotence – often ignored
– Tend to present later
– Larger tumors
– Signs of mass effect
Prolactinoma
• Essential to rule out secondary causes!!
– Drugs which decrease dopamine stores
• Phenothiazines
• Amitriptyline
• Metoclopramide
– Factors inhibiting dopamine outflow
• Estrogen
• Pregnancy
• Exogenous sources
– Hypothyroidism
• If prolactin level > 200, almost always a
prolactinoma (even in a nursing mom)
• Prolactin levels correlate with tumor size in the
macroadenomas
– Suspect another tumor if prolactin low with a large tumor
Prolactinoma
• Diagnosis
– Assess hypersecretion
• Basal, fasting morning PRL levels (normally <20 ug/L)
– Multiple measurements may be necessary
• Pulsatile hormone secretion
• levels vary widely in some individuals with
hyperprolactinemia
– Both false-positive and false-negative results may
be encountered
• May be falsely lowered with markedly elevated PRL levels
(>1000 ug/L)
– assay artifacts; sample dilution is required to measure these
high values accurately
• May be falsely elevated by aggregated forms of circulating
PRL, which are biologically inactive (macroprolactinemia)
– Hypothyroidism should be excluded by measuring
TSH and T4 levels
Prolactinoma
• Treatment
– Medical
• Cabergoline – dopamine receptor agonist
• Bromocriptine - dopamine agonist
– Safe in pregnancy
– Will restore menses
• Decreases both prolactin and tumor size (80%)
– Surgical
• Transsphenoidal surgery – irridation (if pt
cannot tolerate rx)
Quick Quiz!!!
• What type of tumors are most
prolactinomas?
• Prolactin levels >200 almost always
indicate what?
• Do prolactin levels correlate with tumor
size?
MedStudy 2005 - Endocrine
Answer
• What type of tumors are most
prolactinomas? Microadenomas
• Prolactin levels >200 almost always
indicate what? Almost always indicates
prolactinoma
• Do prolactin levels correlate with tumor
size? Yes, in macroadenomas
Growth Hormone
Tumors
• Gigantism
– GH excess before closure of epipheseal
growth plates of long bones
• Acromegaly
– GH excess after closure of epipheseal
growth plates of long bones
– Insidious onset
• Usually diagnosed late
Growth Hormone
Tumors
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May have DM or glucose intolerance
Hypogonadism
Large hands and feet
Large head with a lowering brow and
coarsening features
• Hypertensive – 25%
• Colon polyps
– 3-6 more likely than general population
• Multiple skin tags
Growth Hormone
Tumors
• Diagnosis
– Screen:
• Check for high IGF-I levels (>3 U/ml)
• Remember, levels very high during puberty
– Confirm:
• 100gm glucose load
• Positive: GH levels do not increase to <5ng/ml
• Treatment
– Surgical
– Radiation
– Bromocriptine - temporizing measure
• May decrease GH by 50%
– Octreotide
• For suboptimal response to other treatment
Quick Quiz!!!
• How do you screen for acromegaly?
MedStudy 2005 - Endocrine
Answer
• Check for high IGF-I levels (>3 U/ml)
Pituitary Gland
• Anterior pituitary gland
– Secrete various trophic hormones
– Disease in this region may result in syndromes of
hormone excess or deficiency
• Posterior pituitary gland
– More of a terminus of axons of neurons in the
supraoptic and paraventricular nuclei of the
hypothalamus
– Storehouse for the hormones
– The main consequence of disease in this area is
disordered water homeostasis
Posterior Pituitary Gland
• The Neurohypophysis
• Major blood source: the inferior
hypophyseal arteries
• Directly innervated by hypothalamic
neurons
– (supraopticohypophyseal and
tuberohypophyseal nerve tracts) via the
pituitary stalk
• Sensitive to neuronal damage by lesions that
affect the pituitary stalk or hypothalamus
Posterior Pituitary Gland
• Production of
– Vasopressin (antidiuretic hormone; ADH; AVP)
– Oxytocin
• Vasopressin (antidiuretic hormone;
ADH; AVP)
– Acts on the renal tubules to reduce water loss by
concentrating the urine
– Deficiency causes diabetes insipidus (DI),
characterized by the production of large amounts
of dilute urine
– Excessive or inappropriate production predisposes
to hyponatremia if water intake is not reduced in
parallel with urine output
• Oxytocin
– Stimulates postpartum milk letdown in response to
suckling
Posterior Pituitary Gland
• Vasopressin (Anti Diuretic Hormone)
– Some control via anterior hypothalamus
• Contains separate osmoreceptors which aid in ADH
release and thirst regulation
– Osmotic stimulus
• Sodium
• Mannitol
– Non osmotic factors
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Blood pressure and volume at extremes
Nausea
Angiotensin II
Insulin induced hypoglycemia
Acute hypoxia
Acute hypercapnia
Posterior Pituitary Gland
• Rapidly secreted in direct proportion to serum
osmolality
– Increased with
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Aging
Hypercalcemia
Hypoglycemia
Lithium treatment
Volume contraction
– Decreased with
• Hypokalemia
• Threshold set point
– Increased
• Hypervolemia, Acute hypertension, Corticosteroids
– Decreased
• Pregnancy, Pre-menses, Volume contraction
Diabetes Insipdus
• Etiology
– Deficient AVP can be primary or secondary
• The primary form
– Deficiency in secretion
» Agenesis or irreversible destruction of the
neurohypophysis
» Malformation or destruction of the neurohypophysis by
a variety of diseases or toxins
» Neurohypophyseal DI, Pituitary DI, or Central DI
– Deficiency in action
» Can be genetic, acquired, or caused by exposure to
various drugs
» Nephrogenic DI
– It can be caused by a variety of congenital, acquired, or
genetic disorders
» 50% idiopathic
Diabetes Insipdus
• Gestational DI
– Primary deficiency of plasma AVP
– Result from increased metabolism by an N-terminal
aminopeptidase produced by the placenta
– Signs and symptoms manifest during pregnancy and
usually remit several weeks after delivery
Diabetes Insipdus
• Secondary deficiencies of AVP
– Results from inhibition of secretion by
excessive intake of fluids
• Primary polydipsia
– Dipsogenic DI
» characterized by an inappropriate increase in thirst
» caused by a reduction in the "set" of the
osmoregulatory mechanism.
» association with multifocal diseases of the brain such
as neurosarcoid, tuberculous meningitis, or multiple
sclerosis but is often idiopathic.
– Psychogenic polydipsia
» is not associated with thirst
» polydipsia seems to be a feature of psychosis
– Iatrogenic polydipsia
» results from recommendations of health professionals
or the popular media to increase fluid intake for its
presumed preventive or therapeutic benefits for other
disorders
Diabetes Insipdus
• Secondary deficiencies of AVP
– Antidiuretic response to AVP
• Results from polyuria
• Caused by washout of the medullary
concentration gradient and/or suppression of
aquaporin function.
• Usually resolves 24 to 48 h after the polyuria is
corrected
– Often complicate interpretation of tests commonly
used for differential diagnosis
Diabetes Insipdus
• Pathophysiology
– When secretion or action of AVP is reduced to <80
to 85% of normal
• urine concentration ceases and the rate of output
increases to symptomatic levels
– Primary defect (pituitary, gestational, or
nephrogenic DI)
• Polyuria results in a small (1 to 2%) decrease in body
water and a commensurate increase in plasma
osmolarity and sodium concentration that stimulate thirst
and a compensatory increase in water intake
• Overt signs of dehydration do not develop unless the
patient also has a defect in thirst or fails to drink for some
other reason
Diabetes Insipdus
• Pathophysiology
– Primary polydipsia
• Pathogenesis of the polydipsia and polyuria is the
reverse of that in pituitary, nephrogenic, and gestational
DI
– Excessive intake of fluids slightly increases body water,
thereby reducing plasma osmolarity, AVP secretion, and
urinary concentration.
– Results in a compensatory increase in urinary free-water
excretion that varies in direct proportion to intake
– Clinically appreciable overhydration uncommon
» unless the compensatory water diuresis is impaired by
a drug or disease that stimulates or mimics
endogenous AVP
Diabetes Insipdus
• Clinical Presentation
– Production of abnormally large volumes of dilute
urine
• The 24-h urine volume is >50 mL/kg body weight and the
osmolarity is <300 mosmol/L.
– The polyuria produces symptoms of urinary
frequency, enuresis, and/or nocturia, which may
disturb sleep and cause mild daytime fatigue or
somnolence.
– It is also associated with thirst and a
commensurate increase in fluid intake
(polydipsia).
– Clinical signs of dehydration are uncommon
unless fluid intake is impaired.
Diabetes Insipdus
• Diagnosis
– Verify polyuria
• a 24-h urine output collection
• > 50 mL/kg per day (>3500 mL in a 70-kg man).
– Check osmolarity
• >300 mosmol/L
– due to a solute diuresis and the patient should be
evaluated for uncontrolled diabetes mellitus or other less
common causes of excessive solute excretion
• <300 mosmol/L
– Due to water diuresis and should be evaluated further to
determine which type of DI is present
Diabetes Insipdus
• Diagnosis
– Water deprivation test
• If does not result in urine concentration
before body weight decreases by 5% or
plasma osmolarity/sodium exceed the
upper limit of normal
– (osmolarity >300 mosmol/L, specific gravity
>1.010)
– Primary polydipsia or a partial defect in AVP
secretion or action are largely excluded
– Severe pituitary or nephrogenic DI are the only
remaining possibilities
Diabetes Insipdus
Diagnosis: Neurogenic vs Nephrogenic
• Administer Desmopressin (DDAVP)
• 1 g
• 0.03 ug/kg
• subcutaneously or intravenously
• Measure urine osmolality
– (30,60,120 min)
– 1 to 2 h later
• An increase of >50% indicates severe
pituitary DI
• Smaller or absent response is strongly
suggestive of nephrogenic DI
Diabetes Insipdus
• Treatment
– Neurogenic DI
• DDAVP
• Chlorpropamide (Diabinese)
– Antidiuretic effect can be enhanced by cotreatment with a
thiazide diuretic
– SE: hypoglycemia, disulfiram like reaction to ethanol
– Contraindicated in Gestional DI
– Nephrogenic DI
• Not affected by treatment with DDAVP or chlorpropamide
• May be reduced by treatment with a thiazide diuretic
and/or amiloride in conjunction with a low-sodium diet
• Inhibitors of prostaglandin synthesis (e.g., indomethacin)
are also effective in some patients
– Psychogenic or dipsogenic DI
• there is no effective treatment
Syndrome of Inappropriate
ADH secretion
• Etiology
– CNS
• Lesions, Inflammatory disease
• Trauma, psychosis
– Drugs
• Stimulate AVP release
– Nicotine, phenothiazines, TCAs, SSRIs
• Chlorpropamide, clofibrate, carbamazepine,
cyclophosphamide, vincristine
– Pulmonary
• Infection
• Mechanical/ventilatory issue
Syndrome of Inappropriate
ADH secretion
• Pathophysiology
– Excessive AVP production resulting in
decreased volume of highly concentrated
urine
– Water retention
– Decreased plasma osmolarity
– Decreased plasma Na
Syndrome of Inappropriate
ADH secretion
• Clinical Presentation
– Acute
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Water intoxication
Headache, confusion
Nausea, vomiting
Anorexia
Coma, convulsions
– Chronic
• May be asymptomatic
Syndrome of Inappropriate
ADH secretion
• Diagnosis
– Diagnosis of exclusion
– AVP level inappropriately elevated relative
to plasma osmolality
Syndrome of Inappropriate
ADH secretion
• Treatment
– Acute
• Fluid restriction
• Hypertonic saline
– Central myelinolysis
– Chronic
• Demeclocyline 150-300mg PO TID-QID
– Reversible Nephrogenic DI
Treatment Guidelines
• See Handout
References
• Harrison's Principles of Internal
Medicine - 16th Ed. (2005)
• Up to Date
• Med Study – Endocrine
• Mayo Clinic Board Review
Questions
True or False
The pituitary:
1. Pituitary tumors are usually
macroadenomas.
2. Lack of galactorrhea essentially rules out a
prolactinoma.
3. Prolactin levels correlate with the size of a
prolactinoma
4. Prolactin level of 230 in a nursing woman is
probably due to a prolactinoma
5. An enlarged sella tursica can be seen in a
hypothyroid patient.
Answers
The pituitary:
1. Pituitary tumors are usually
macroadenomas. – True
2. Lack of galactorrhea essentially rules out a
prolactinoma. – False
3. Prolactin levels correlate with the size of a
prolactinoma – True
4. Prolactin level of 230 in a nursing woman is
probably due to a prolactinoma – True
5. An enlarged sella tursica can be seen in a
hypothyroid patient. – True
MedStudy 2005 - Endocrine
• A 24 year old woman complains of fatigue
and malaise. She gave birth to a healthy
infant 4 months before presentation. She
did not breastfeed. Menses have
subsequently been irregular and
infrequent, representing a change from
before pregnancy. The family history is
notable for a sister who has Hashimoto
thyroiditis. The pregnancy test is negative,
and the serum level of prolactin is normal.
Of interest, TSH is 0.9mIU/L (normal, 0.35.0) and free thyroxine is 0.8ng/dL
(normal, 0.8-1.4). The results of MRI of
the pituitary are reported as normal. The
next step would be to:
•A) Start thyroxine replacement therapy
•B) Request a neurosurgeon to perform a
biopsy of the pituitary
•Perform a water deprivation test
•Perform a 1 µg corticotropin (ACTH)
stimulation test
•Measure IGF-1
•A) Start thyroxine replacement therapy
•B) Request a neurosurgeon to perform a
biopsy of the pituitary
•C) Perform a water deprivation test
•D) Perform a 1 µg corticotropin (ACTH)
stimulation test
•E) Measure IGF-1
A 38-year-old woman is referred to you by her
gynecologist. She first presented to her gynecologist
4.5 years ago with amenorrhea of 3 years’ duration
and galactorrhea of 1 year’s duration. She had been
taking no medications, and her initial physical
examination was unremarkable except for
expressible galactorrhea bilaterally. A routine
chemistry screen was normal; her T4 level was 7.8
µg/dL, serum TSH was 1.4 µU/mL, and prolactin
level was 48.2 ng/mL.
After taking bromocriptine for 2 months, her prolactin
level was 19 ng/mL, at which point her galactorrhea
ceased and she had her first menstrual period in 3
years. She continued to take bromocriptine over the
next 4 years; her prolactin level remained less than
20 ng/mL, and she continued to have regular
periods. However, she stopped taking her
bromocriptine 6 months ago and is now having
progressively worse headaches.
Her prolactin level is now 60.5 ng/mL, and a
visual field examination shows a small
superotemporal field cut in the right eye. A
computed tomographic (CT) scan shows a
2.4-cm ´ 1.6-cm sellar mass with
considerable suprasellar extension. She is
now referred to you for further management.
What is the most likely diagnosis?
(A) Prolactinoma
(B) Clinically nonfunctioning pituitary adenoma
(C) Metastatic cancer to the sella
(D) Craniopharyngioma
What is the most likely diagnosis?
(A) Prolactinoma
(B) Clinically nonfunctioning pituitary adenoma
(C) Metastatic cancer to the sella
(D) Craniopharyngioma