ENDOCRINOLOGY%20BOARD%20REVIEW

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ENDOCRINOLOGY BOARD REVIEW

• Presented by Med/Peds PGY III Class

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ENDOCRINOLOGY Disorders of the Hypothalamic
Pituitary Axis

• K. Dionne Posey, MD, MPH

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ENDOCRINOLOGY

• Pituitary Disorders
• Thyroid Disorders
• Adrenal Disorders
• Gonadal Disorders
• Calcium Disorders
• Lipid Disorders

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HypothalamicPituitary Axis
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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

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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

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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
• Prolactin (PRL)
• Growth hormone (GH)
• Adrenocorticotropin hormone (ACTH)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Thyroid-stimulating hormone (TSH)

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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

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Hypopituitarism
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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)

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ACTH Deficiency

• Results in hypocortisolism
• Malaise
• Anorexia
• Weight-loss
• Gastrointestinal disturbances
• Hyponatremia
• Pale complexion
• Unable to tan or maintain a tan
• No features of mineralocorticoid deficiency
• Aldosterone secretion unaffected

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TSH Deficiency

• Hypothyroidism
• Atrophic thyroid gland

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Prolactin Deficiency

• Inability to lactate postpartum
• Often 1st manifestation of Sheehan syndrome

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Growth Hormone Deficiency

• Adults
• Often asymptomatic
• May complain of
• Fatigue
• Degrees exercise tolerance
• Abdominal obesity
• Loss of muscle mass
• Children
• GH Deficiency
• Constitutional growth delay

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Hypopituitarism

• Etiology
• Anterior pituitary diseases
• Deficiency one or more or all anterior pituitary
  hormones
• Common causes
• Primary pituitary disease
• Hypothalamic disease
• Interruption of the pituitary stalk
• Extrasellar disorders

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Hypopituitarism

• Primary pituitary disease
• Tumors
• Pituitary surgery
• Radiation treatment
• Hypothalamic disease
• Functional suppression of axis
• Exogenous steroid use
• Extreme weight loss
• Exercise
• Systemic Illness

• Interruption of the pituitary stalk
• Extrasellar disorders
• Craniopharyngioma
• Rathke pouch

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Hypopituitarism

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Hypopituitarism

• Developmental and genetic causes
• Dysplasia
• Septo-Optic dysplasia
• Developmental hypothalamic dysfunction
• Kallman Syndrome
• Laurence-Moon-Bardet-Biedl Syndrome
• Frohlich Syndrome (Adipose Genital Dystrophy)

• Acquired causes
• Infiltrative disorders
• Cranial irradiation
• Lymphocytic hypophysitis
• Pituitary Apoplexy
• Empty Sella syndrome

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Hypopituitarism Developmental and Genetic causes

• Septo-Optic dysplasia
• Kallman Syndrome
• Laurence-Moon-Bardet-Biedl Syndrome
• Frohlich Syndrome (Adipose Genital Dystrophy)

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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

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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

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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

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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

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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

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Hypopituitarism

• Acquired causes
• Infiltrative disorders
• Cranial irradiation
• Lymphocytic hypophysitis
• Pituitary Apoplexy
• Empty Sella syndrome

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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

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Hypopituitarism Acquired

• Pituitary Apoplexy
•  Hemorrhagic infarction of a pituitary
  adenoma/tumor
• Considered a neurosurgical emergency
• Presentation
• 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

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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

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Quick Quiz!!!

• When should you suspect pituitary apoplexy?

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Answer

• Suspect in patient presenting with
• Variable onset of severe headache
• Nausea and vomiting
• Meningismus
• Vertigo
• / - Visual defects
• / - Altered consciousness

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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

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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

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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

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Hypopituitarism

• Treatment
• Hormone replacement therapy
• usually free of complications
• Treatment regimens that mimic physiologic hormone
  production
• allow for maintenance of satisfactory clinical
  homeostasis

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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 MalesTestosterone enanthate (200 mg IM every 2 wks)Testosterone skin patch (5 mg/d)FemalesConjugated estrogen (0.65-1.25 mg qd for 25days)Progesterone (5-10 mg qd) on days 16-25Estradiol 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
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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

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Pituitary Tumors
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Pituitary Tumors

• Microadenoma lt 1 cm
• Macroadenoma gt 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

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Pituitary Tumors

• Diagnosis
• Check levels of all hormones produced
• Check levels of target organ products
• Treatment
• 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

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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

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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

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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.

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Quick Quiz!!!

• How does prolactin differ from LH/FSH in regard
  to hypothalamic control?

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Answer

• Tonic hypothalamic inhibition by Dopamine

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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

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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

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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 gt 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

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Prolactinoma

• Diagnosis
• Assess hypersecretion
• Basal, fasting morning PRL levels (normally lt20
  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 (gt1000 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

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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)

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Quick Quiz!!!

• What type of tumors are most prolactinomas?
• Prolactin levels gt200 almost always indicate
  what?
• Do prolactin levels correlate with tumor size?

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Answer

• What type of tumors are most prolactinomas?
  Microadenomas
• Prolactin levels gt200 almost always indicate
  what? Almost always indicates prolactinoma
• Do prolactin levels correlate with tumor size?
  Yes, in macroadenomas

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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

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Growth Hormone Tumors

• 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

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Growth Hormone Tumors

• Diagnosis
• Screen
• Check for high IGF-I levels (gt3 U/ml)
• Remember, levels very high during puberty
• Confirm
• 100gm glucose load
• Positive GH levels do not increase to lt5ng/ml
• Treatment
• Surgical
• Radiation
• Bromocriptine - temporizing measure
• May decrease GH by 50
• Octreotide
• For suboptimal response to other treatment

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Quick Quiz!!!

• How do you screen for acromegaly?

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Answer

• Check for high IGF-I levels (gt3 U/ml)

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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

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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

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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

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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
• Blood pressure and volume at extremes
• Nausea
• Angiotensin II
• Insulin induced hypoglycemia
• Acute hypoxia
• Acute hypercapnia

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Posterior Pituitary Gland

• Rapidly secreted in direct proportion to serum
  osmolality
• Increased with
• Aging
• Hypercalcemia
• Hypoglycemia
• Lithium treatment
• Volume contraction
• Decreased with
• Hypokalemia
• Threshold set point
• Increased
• Hypervolemia, Acute hypertension, Corticosteroids
• Decreased
• Pregnancy, Pre-menses, Volume contraction

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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

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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

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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

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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

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Diabetes Insipdus

• Pathophysiology
• When secretion or action of AVP is reduced to lt80
  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

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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

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Diabetes Insipdus

• Clinical Presentation
• Production of abnormally large volumes of dilute
  urine
• The 24-h urine volume is gt50 mL/kg body weight
  and the osmolarity is lt300 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.

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Diabetes Insipdus

• Diagnosis
• Verify polyuria
• a 24-h urine output collection
• gt 50 mL/kg per day (gt3500 mL in a 70-kg man).
• Check osmolarity
• gt300 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
• lt300 mosmol/L
• Due to water diuresis and should be evaluated
  further to determine which type of DI is present

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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 gt300 mosmol/L, specific gravity
  gt1.010)
• Primary polydipsia or a partial defect in AVP
  secretion or action are largely excluded
• Severe pituitary or nephrogenic DI are the only
  remaining possibilities

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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 gt50 indicates severe pituitary DI
• Smaller or absent response is strongly suggestive
  of nephrogenic DI

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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

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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

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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

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Syndrome of Inappropriate ADH secretion

• Clinical Presentation
• Acute
• Water intoxication
• Headache, confusion
• Nausea, vomiting
• Anorexia
• Coma, convulsions
• Chronic
• May be asymptomatic

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Syndrome of Inappropriate ADH secretion

• Diagnosis
• Diagnosis of exclusion
• AVP level inappropriately elevated relative to
  plasma osmolality

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Syndrome of Inappropriate ADH secretion

• Treatment
• Acute
• Fluid restriction
• Hypertonic saline
• Central myelinolysis
• Chronic
• Demeclocyline 150-300mg PO TID-QID
• Reversible Nephrogenic DI

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Treatment Guidelines

• See Handout

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References

• Harrison's Principles of Internal Medicine - 16th
  Ed. (2005)
• Up to Date
• Med Study Endocrine
• Mayo Clinic Board Review

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Questions
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True or False

• The pituitary
• Pituitary tumors are usually macroadenomas.
• Lack of galactorrhea essentially rules out a
  prolactinoma.
• Prolactin levels correlate with the size of a
  prolactinoma
• Prolactin level of 230 in a nursing woman is
  probably due to a prolactinoma
• An enlarged sella tursica can be seen in a
  hypothyroid patient.

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Answers

• The pituitary
• Pituitary tumors are usually macroadenomas.
  True
• Lack of galactorrhea essentially rules out a
  prolactinoma. False
• Prolactin levels correlate with the size of a
  prolactinoma True
• Prolactin level of 230 in a nursing woman is
  probably due to a prolactinoma True
• An enlarged sella tursica can be seen in a
  hypothyroid patient. True

103

• 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, 0.3-5.0) 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

104

• 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

105

• 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

106

• 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 years
  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.

107

• 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

108

• What is the most likely diagnosis?
•  
• (A) Prolactinoma
• (B) Clinically nonfunctioning pituitary adenoma
• (C) Metastatic cancer to the sella
• (D) Craniopharyngioma