ENDOCRINOLOGY
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  • Stimulate production of IGFs Suppressed by hyperglycemia Stimulated by hypoglycemia GH bone age < chron age CGD
  • Pituitary adenoma Lymphocytic hypophysitis
  • Pituitary adenoma. Coronal T1-weighted postcontrast MR image shows a homogeneously enhancing mass ( arrowheads ) in the sella turcica and suprasellar region compatible with a pituitary adenoma; the small arrows outline the carotid arteries.
  • Adenoma Craniopharyngioma
  • Craniophayrngioma
  • Prolactin
  • Insensible losses ~500ml/day; so intake should be ~500 less than UO Quadraparesis, ataxia, abn extraocc movements 3% saline </= 0.05ml/kg/min; stat check NA q 2hr Stop once inreases by 12mmol or to 130mmol/L Watch UO
  • Lymphocytic Hypophysitis

ENDOCRINOLOGY ENDOCRINOLOGY Presentation Transcript

  • ENDOCRINOLOGY BOARD REVIEW Presented by Med/Peds PGY III Class
  • ENDOCRINOLOGY Disorders of the Hypothalamic – Pituitary Axis K. Dionne Posey, MD, MPH
  • ENDOCRINOLOGY
    • Pituitary Disorders
    • Thyroid Disorders
    • Adrenal Disorders
    • Gonadal Disorders
    • Calcium Disorders
    • Lipid Disorders
  •  
  • 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:
        • 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
      • 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 1 st manifestation of Sheehan syndrome
  • 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
  •  
  • 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
  • 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
  • Hypopituitarism
  • 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
  • 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:
        • 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?
  • Answer
    • Suspect in patient presenting with
        • 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 Intranasal desmopressin (5-20 ug twice daily) Oral 300-600 ug qd Vasopressin Adults: Somatotropin (0.3-1.0 mg SC qd) Children: Somatotropin [0.02-0.05 (mg/kg per day)] GH 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 FSH/LH L-Thyroxine (0.075-0.15 mg daily) TSH 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.) ACTH Hormone Replacement Trophic Hormone Deficit
  • 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
      • 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 micro adenoma
    • 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?
  • 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
    • 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?
  • 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
        • 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
        • 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 &quot;set&quot; 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
        • 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:
    • 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.
  • 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
    • 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:
    • 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