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Pituitary Gland

- Anterior pituitary releases 5 hormones – TSH, PRL,ACTH, GH, FSH, LH


- Stimulatory releasing factors from hypothalamus - TRH, CRH, GHRH, GnRH
- Inhibitory hypothalamic influences comprise PIF and somatostatin
- Anterior lobe (adenohypophysis)
o Somatotrophs, producing GH
o Mammosomatotrophs, producing GH and PRL
o Lactotrophs, producing PRL
o Corticotrophs, producing ACTH, POMC and MSH
o Thyrotrophs, producing TSH
o Gonadotrophs, producing FSH and LH
- Posterior lobe (neurohypophysis)
o Oxytocin
o Antidiuretic hormone
- Clinical Manifestations of Pituitary Disease
o Hyperpituitarism
 From excess secretion of trophic hormones
 Pituitary adenoma, hyperplasia and carcinomas of anterior pituitary, secretion of hormones by non-pituitary tumors, and certain hypothalamic
disorders
o Hypopituitarism
 From deficiency of trophic hormones
 Ischemic injury, surgery or radiation, inflammatory reactions, and nonfunctional pituitary adenomas
o Local mass effects
 Radiographic abnormalities of the sella turcica
 Visual field abnormalities- bitemporal hemianopsia
 Elevated intracranial pressure
 Pituitary apoplexy
- Pituitary Adenomas
o Most common cause of hyperpituitarism
o Classified on the basis of hormones produced by tumor cells
o Some can secrete 2 hormones (GH + PRL) , can be plurihormonal
o Functional or nonfunctioning
o Large pituitary adenomas may cause hypopituitarism by encroaching on and destroying the adjacent anterior
pituitary parenchyma
o Peak incidence - 35 to 60 years of age
o Microadenomas (<1 cm in dia) and Macroadenomas (> 1cm)
o Mostly clinically silent microadenomas (“pituitary incidentaloma”)
o G-protein mutations : ↓GTPase activity of Gsα - constitutive activation of Gsα, persistent generation of cAMP, and unchecked cellular proliferation
o Inherited genetic defects: 5% of cases, MEN1, CDKN1B, PRKAR1A, and AIP
o Morphology
 Soft and well-circumscribed
 Small adenomas confined to the sella turcica
 Larger lesions extend superiorly into suprasellar region - compress the optic chiasm and cranial nerves
 Uniform, polygonal cells arrayed in sheets or cords
 Cellular monomorphism + absence of reticulin network (distinguish adenomas from non-neoplastic anterior pituitary parenchyma)
o Ex. A 20-year-old man’s closest friends tell him he looks different now than a year ago, with coarse features. He bought new shoes with his usual size and they
do not fit. A year later his 23-year-old brother has similar problems. Both of them have hyperglycemia. Which of the following genetic alterations is most likely
present in both brothers? Germline mutation of AIP
o Ex. A 30-year-old woman complains of headache, visual disturbances, deepening of the voice, and generalized weakness. She reports amenorrhea for the past
year and states that she recently required a larger shoe size. Laboratory studies show impaired glucose tolerance. What other procedure would be useful for
establishing your diagnosis? MRI of the sella turcica.
- Lactotroph Adenoma (Prolactinoma)
o Most frequent hyperfunctioning pituitary adenoma (30%)
o Sparsely granulated lactotroph adenomas
 More common, chromophobic cells with juxtanuclear localization of the transcription factor PIT-1
o Densely granulated lactotroph adenomas
 Diffuse cytoplasmic PIT-1 expression localization
o Propensity to undergo dystrophic calcification – isolated psammoma bodies to “pituitary stone”
o Hyperprolactinemia
o Clinical Course
 Prolactinemia - Amenorrhea, Galactorrhea, Loss of Libido, and Infertility
 Diagnosed more readily in women, 20 and 40 years (sensitivity of menses to disruption by
hyperprolactinemia)
 Treated by surgery or bromocriptine (dopamine receptor agonist)
o Ex. A 25-year-old woman has noted breast secretions for the past month. She is not breastfeeding and has never been
pregnant. She has not menstruated for the past 5 months. Physical examination yields no abnormal findings. MRI of the brain shows a 0.7-cm mass within the
sella turcica. Which of the following additional complications is she most likely to have? Infertility
o Ex. A 35-year-old woman with a history of schizophrenia complains of headaches, visual disturbances, and irregular menses for 9 months. On physical
examination the breasts are firm and tender. MRI shows enlargement of the anterior pituitary (arrow). Which of the following is the most likely cause of
pituitary enlargement in this patient? Lactotrope adenoma
- Hypersecretion of Prolactin
o In women
 Secondary amenorrhea (loss of menses)
 Prolactin inhibits GnRH
 Decrease in FSH/LH causes decrease in estrogen synthesis in the ovaries
 Galactorrhea in non-nursing women
o In men
 Impotence - decreased libido (decrease in testosterone from decrease in serum LH)
 Headache (tumors tend to be larger in men than in women)
 Not enough estrogen-dependent breast tissue to produce galactorrhea
- Hyperprolactinemia
o Physiologic hyperprolactinemia
 Pregnancy, suckling in lactating women, response to stress
o Pathologic hyperprolactinemia
 Prolactin-secreting pituitary adenomas
 Lactotroph hyperplasia (loss of dopamine-mediated inhibition of prolactin)
 Damage of the dopaminergic neurons of the hypothalamus
 Damage of the pituitary stalk (head trauma)
 Exposure to drugs that block dopamine receptors on lactotroph cells
o Mass in the suprasellar compartment (pituitary adenoma) *
 May disturb the normal inhibitory influence of the hypothalamus on prolactin secretion
o Renal failure and hypothyroidism
- Somatotroph Adenomas
o Second most common type of functioning pituitary adenoma
o Densely granulated and sparsely granulated subtypes
o Bihormonal mammosomatotroph adenomas (GH + prolactin)
o ↑GH stimulates the hepatic secretion of IGF-1
 Gigantism in children and acromegaly in adults
 Gonadal dysfunction, diabetes mellitus, generalized muscle weakness, hypertension, arthritis, congestive heart failure, ↑risk of gastrointestinal
cancers
o Diagnosis
 ↑GH, IGF-1 (most sensitive)
 Failure to suppress GH production in response to an oral load of glucose
o Treatment – surgical removal or somatostatin analogs
- Hypersecretion of GH
o Primary: ↑ production & blood level of GH & somatomedins
o Secondary: ↑ GHRH secretion from Hypothalamus
o ↑ GH secretion before ossification of the epiphyseal growth plates in children - Gigantism
o ↑ GH secretion in adults – Acromegaly
- Hypersecretion of GH in children – Gigantism
o Inappropriate, continuing excessive stimulation of somatic & visceral growth
 ↑ linear and radial bone growth, tall stature, increase in body size
o Disproportions and skeletal deformities
 ↑ hand and foot size , deformation of the chest wall
o Metabolic: hyperglycemia, diabetes mellitus
o Treatment – Somatostatin analogues
- Hypersecretion of GH in adults – Acromegaly
o Excessive growth of tissues capable of growth during adulthood
 Soft tissues: thick skin with pronounced pores, ↑ size of viscera, lips, tongue, nose
 ↑ protein, ↓ subcutaneous fat
 Bones in which cartilage is still left
 Acral parts of the hands and feet (hence the term acromegaly)
 Membranous bones: cranium, lower jaw, nose, supraorbital ridges, portions of the vertebrae
o Acromegalic face: enlarged facial structures
 Protrusion of lower jaw
 Enlarged (bulbous) nose
 Enlarged tongue (macroglossia)
 Enlarged forehead, bony ridges above eyes
o Ex. A 41-year-old woman notices that her gloves from the previous winter no longer fit her hands. Her facial features have become coarse in the past year,
and her voice seems deeper. On physical examination, her blood pressure is 140/90 mm Hg. There is decreased sensation to pinprick over the palms in the
distribution of her thumb and first two fingers. A radiograph of the foot shows an increased amount of soft tissue beneath the calcaneus. A chest radiograph
shows cardiomegaly. Laboratory studies indicate a fasting serum glucose level of 138 mg/dL and hemoglobin A1c level of 8.6%. Which of the following
additional test results is most likely to indicate the cause of her physical and laboratory findings? Failure of growth hormone suppression
o Ex. A 48-year-old man presents with recurrent headaches andarthritic pain in his knees of 9 months in duration. He notes that this hat size has recently
increased. He also states that he suffers from erectile dysfunction. His past medical history is significant for kidney stones 2 years ago. Physical examination
reveals a blood pressure of 170/100 mm Hg. The patient is observed to have coarse facial features and a goiter. Urinalysis reveals glucosuria and
hypercalciuria. Which of the following is the most likely explanation for this patient’s clinical presentation? Excess growth hormone secretion
 Why does the patient described in Question 11 suffer from erectile dysfunction? Excess prolactin secretion by the pituitary.
- Corticotroph Adenomas
o Excess production of ACTH leads to adrenal hypersecretion of cortisol (hypercortisolism)
o Ex. A 60-year-old woman with small cell carcinoma of the lung notes rounding of her face, upper truncal obesity, and muscle weakness. Physical examination
reveals thin, wrinkled skin, abdominal striae, and multiple purpuric skin lesions. The patient’s blood pressure is 175/95 mm Hg. Laboratory studies will likely
show elevated serum levels of which of the following hormones? Corticotropin
o Microadenomas
 Basophilic (densely granulated) or chromophobic (sparsely granulated)
 Both stain positive with PAS (presence of carbohydrate in POMC)
 Immunoreactivity for POMC and its derivatives (ACTH and β-endorphin)
o Cushing disease
 Hypercortisolism due to excessive production of ACTH by the pituitary
o Nelson syndrome
 Large destructive pituitary adenomas develop in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome
 Mass effects of pituitary mass
 Hyperpigmentation
- Gonadotroph (LH and FSH-producing) adenomas
o Mostly non functioning adenomas
o Middle aged individuals with neurologic symptoms (impaired vision, headaches, diplopia, or pituitary apoplexy)
o Decreased energy and libido in men (due to reduced testosterone)and amenorrhea in premenopausal women
o Immunoreactivity for the common gonadotropin α-subunit and the specific β-FSH and β-LH subunits
o FSH is usually the predominant secreted hormone
- Other adenomas
o Thyrotroph (TSH-producing) adenomas
 Uncommon, 1% of all pituitary tumors
o Nonfunctioning pituitary adenomas
 Silent variants or null-cell adenomas
 25 to 30% of all pituitary tumors
 Immunohistochemical staining for hormones or by biochemical demonstration of cell type-specific transcription factors
 Symptoms stem from mass effects
 Can lead to hypopituitarism
 Slowly due to gradual enlargement of the adenoma
 Abruptly because of acute intratumoral hemorrhage (pituitary apoplexy)
 Ex. A 39-year-old woman has had no menstrual periods for the past year, along with malaise, cold intolerance, and loss of body hair. She has had
headaches for the past 5 months. On physical examination her lateral visual fields are reduced. She is most likely to have a neoplasm composed of
which of the following cell types? Chromophobe
 She has a nonfunctioning (null-cell) pituitary adenoma that has enlarged to compress and obliterate the normal adenohypophyseal
cells resulting in hypopituitarism; the adenoma also presses on the optic chiasm, producing bitemporal hemianopsia. About a fourth of
all pituitary tumors are nonfunctioning.
- Pituitary carcinoma
o < 1% of pituitary tumors
o Presence of craniospinal or systemic metastases
o Most are functional (Prolactin and ACTH being the most common)
o Metastases usually appear late in the course, following multiple local recurrences
- Hypopituitarism
o ↓ Secretion of pituitary hormones, diseases of the hypothalamus or of the pituitary
 Primary hypopituitarism (pituitary dysfunction)
 Approximately 75% of the gland must be destroyed
 Secondary hypopituitarism (hypothalamic dysfunction)
 Decreased hypothalamic releasing factors
 Hypopituitarism + diabetes insipidus (Hypothalamic origin)
o Congenital or acquired
 Tumors and other mass lesions – Non functioning  Pituitary apoplexy
adenoma  Rathke cleft cyst
 Ischemic necrosis of the pituitary and Sheehan  Empty sella syndrome
syndrome  Hypothalamic lesions
 Traumatic brain injury and subarachnoid  Inflammatory disorders and infections
hemorrhage  Sickle cell anemia (HbSS)
 Pituitary surgery or radiation  Genetic defects
- Pituitary apoplexy
o Sudden onset of neurologic dysfunction caused by hemorrhage into the pituitary gland
o Predisposing factors
 Trauma, pregnancy (Sheehan postpartum necrosis, a non-tumorous cause), treatment of a prolactinoma with bromocriptine
o Sudden onset of excruciating headache, diplopia due to pressure on the oculomotor nerves, and hypopituitarism
o Can cause cardiovascular collapse, loss of consciousness, sudden death
o True neurosurgical emergency
- Sheehan syndrome
o Postpartum necrosis of the anterior pituitary
 During pregnancy the anterior pituitary enlarges to twice its normal size (not accompanied by an increase in blood supply from the low-pressure
venous system)
 Any further reduction in blood supply caused by obstetric hemorrhage or shock may precipitate infarction of the anterior lobe
 Hypovolemic shock causes infarction, sudden cessation of lactation (due to loss of prolactin)
 Eventual development of hypopituitarism
o Posterior pituitary receives its blood directly from arterial branches, and is less susceptible to ischemic injury
o Ex. A 21-year-old woman delivers a term infant after an uncomplicated pregnancy. The placenta cannot be delivered, however, and there is substantial
hemorrhage, requiring transfusion of 10 U of packed RBCs. She must undergo a hysterectomy. Over the next 3 months, she is unable to produce sufficient
milk to breastfeed her infant, and she becomes increasingly fatigued. Laboratory studies show Na+, 134 mmol/L; K+, 5.2 mmol/L; Cl–, 88 mmol/L; CO2, 23
mmol/L; glucose, 59 mg/dL; calcium, 9.3 mg/dL; phosphorus, 3.5 mg/ dL; and creatinine, 0.9 mg/dL. Over the next 5 months, her menstrual cycles do not
return. Which of the following laboratory findings is now most likely to be reported in this woman? Failure of growth hormone stimulation
 Sheehan syndrome, or postpartum pituitary necrosis,is caused by pituitary enlargement during pregnancy, causing its blood supply to be more
tenuous so that intrapartum hypotension with obstetric bleeding complications (e.g., the placenta accreta in this patient) predisposes to
infarction. The anterior pituitary is at greater risk than the posterior pituitary. The laboratory findings in this patient suggest adrenal insufficiency,
and her inability to breastfeed is caused by lack of prolactin; loss of menstrual cycles suggests that follicle-stimulating hormone and luteinizing
hormone levels are deficient.
o Ex. A 21-year-old woman experiences abruptio placentae with severe bleeding during the delivery of a term fetus. Five months later, she presents with
profound lethargy, pallor, muscle weakness, failure of lactation, and amenorrhea. Which of the following pathologic findings is expected in this patient?
Infarction of the pituitary
Hypothalamic Suprasellar Tumors
- Craniopharyngioma
o Arises from vestigial remnants of Rathke pouch (derived from the oral ectoderm. It develops into the anterior lobe of the pituitary gland)
o 1 to 5% of intracranial tumors, mostly suprasellar
o Bimodal age distribution - one peak in childhood (5 to 15 years) and a second peak in adults 65 years or older
o Malignant transformation of craniopharyngiomas into squamous carcinomas is exceptionally rare and usually occurs after irradiation
o Children may present with growth retardation due to pituitary hypofunction and GH deficiency - most common cause of hypopituitarism in children
o Headaches and visual disturbances in adults
o Commonly causes bitemporal hemianopia (compresses optic chiasm)
o May cause central diabetes insipidus
o Abnormalities of the WNT signaling pathway
o Adamantinomatous Craniopharyngioma (children)
 Radiologically demonstrable calcifications
 Nests or cords of stratified squamous epithelium embedded in a spongy “reticulum” that becomes
more prominent in the internal layers
 “Palisading” of the squamous epithelium at the periphery
 Compact, lamellar keratin formation (“wet keratin”)
 Cyst formation, fibrosis, and chronic inflammation
 Cysts contain cholesterol-rich, thick brownish yellow fluid “machine oil”
o Papillary Craniopharyngioma (adults)
 Calcification is rare
 Solid sheets and papillae lined by well-differentiated squamous epithelium
 No keratin, calcification or cysts
 No peripheral palisading or spongy reticulum
o Patients with craniopharyngiomas, especially those less than 5 cm in diameter, have an excellent recurrence-free and overall survival
o Ex. A 23-year-old man has experienced headaches, polyuria, and visual problems for the past 3 months. On physical examination, he has bilateral temporal
visual field deficits. CT scan of the head shows a large, partially calcified, cystic mass occupying the sellar and suprasellar areas. Laboratory findings show a
serum prolactin concentration of 60 ng/mL and serum sodium level of 152 mEq/L. Serum calcium, phosphate, and glucose levels are normal. The mass is
excised, and histologic examination shows a mixture of squamous epithelial elements and lipid-rich debris containing cholesterol crystals. Which of the
following lesions is most consistent with the clinical and laboratory findings in this patient? Craniopharyngiomas
o Ex. A 14-year-old boy presents with 3 months of lethargy, headaches, and muscle weakness. His parents note that he
drinks water excessively. His vital signs are normal. A 24-hour urine collection shows polyuria. The fasting blood sugar is
normal. An X-ray fi lm of the brain reveals suprasellar calcifi - cation. An autopsy specimen of a similar case is shown in the
image. Which of the following neoplasms is the most likely cause of polyuria in this patient? Craniopharyngiomas
- Empty sella syndrome
o Any condition or treatment that destroys part or all of the pituitary gland
o Ablation of the pituitary by surgery or radiation
o Primary empty sella:
 A defect in the diaphragma sella allows the arachnoid mater and CSF to herniate into the sella, expanding the sella and compressing the pituitary
 Obese women with a history of multiple pregnancies, hypertension
 Visual field defects and endocrine anomalies
 Hypopituitarism
o Secondary empty sella:
 A mass enlarges the sella and is then either surgically removed or undergoes infarction, leading to loss of pituitary function
o Ex. A 39-year-old G2, P2 woman, whose last pregnancy was 14 years ago, has had absent menstrual cycles for 6 months. She also reports expression of milk
from her breasts. On physical examination, she is normotensive. She is 150 cm tall and weighs 63 kg (body mass index 28). Secondary sex characteristics are
normal. Laboratory testing indicates that β-human chorionic gonadotropin level is normal. She has a normal growth hormone stimulation test. CT scan of the
head shows no abnormalities of bone and no hemorrhage. Brain MRI shows fluid density within a normal-sized sella turcica. What is the most likely diagnosis?
Empty sella syndrome
- Deficiency of Gonadotropins (FSH, LH)
o Children have delayed puberty
o Adult females have secondary amenorrhea; produces osteoporosis, hot flashes (lack of estrogen), decreased libido (sexual desire)
o Males have impotence, due to decreased libido from decreased testosterone
o GnRH stimulation test: no significant increase of FSH/LH in hypopituitarism; eventual increase of FSH/LH in hypothalamic disease
- Deficiency of Growth Hormone
o Decreased GH decreases synthesis and release of IGF-1
o Children have growth delay: delayed fusion of epiphyses; bone growth does not match the age of the child
o Adults have hypoglycemia: decreased gluconeogenesis; loss of muscle mass; increased adipose around the waist
o Arginine and sleep stimulation tests: no increase in GH or IGF-1
o GH overall effect
 enhances body protein, uses up fat stores, conserves carbohydrates
- Hyposecretion of GH in children – Pituitary Dwarfism
o Effects on physical growth and development
 Stunted somatic growth, delayed bone maturation and short stature, ↓ growth of visceral organs
 Normal body proportions
 No physical deformities
 No mental retardation
 ↓ Sexual development, baby-like face
 ↓ Muscular development (↓ protein anabolism)
 Obesity (↑ fat deposition, ↓ lipolysis)
 Low fasting blood sugar, delayed recovery from insulin hypoglycemia
o Treatment
 Replacement therapy with human Growth Hormone (recombinant DNA technology)
- The African pygmy and the Levi-Lorain dwarfs lack the ability to produce somatomedin C (IGF-1)in response to growth hormone
- Achondroplasia is disproportionate dwarfism with short limbs caused by mutations in the FGFR3 gene
- Deficiency of TSH
o Secondary hypothyroidism: decreased serum T4 and TSH
o Cold intolerance, constipation, weakness
o No increase in TSH after TRF stimulation
- Deficiency of ACTH
o Metyrapone test
o Stimulation test of pituitary ACTH and adrenal gland reserve
o Metyrapone inhibits adrenal 11-hydroxylase, which causes a decrease in cortisol and a corresponding increase in plasma ACTH (pituitary) and 11-
deoxycortisol (adrenal), which is proximal to the enzyme block
o In hypopituitarism, neither ACTH or 11-deoxycortisol are increased
o In adrenal disease, ↑ ACTH but ↓11-deoxycortisol
 Schematic of the metyrapone test: a normal response (A) and the response expected in hypopituitarism (B)
 A: Metyrapone blocks 11-hydroxylase in the adrenal cortex. This decreases cortisol leading to an increase in ACTH and 11-deoxycortisol
 B: A decrease in cortisol does not increase pituitary ACTH indicating hypopituitarism as the cause of hypocortisolism. Because ACTH is not
increased, there is no increase in 11-deoxycortisol proximal to the enzyme block.
Posterior Pituitary Syndromes
- ADH: Control of secretion
o Factors that stimulate ADH secretion
 Increased blood osmolarity OR decreased blood volume
 Stress, pain, trauma, anxiety
 Acetylcholine, Nicotine, Morphine, Anesthetics
o Factors that inhibit ADH secretion
 Decreased blood osmolarity OR Increased blood volume
 Ethanol (drinking causes frequent, copious urination and may also be responsible for the thirst and headache of hangovers)
- Diabetes insipidus
o ADH deficiency leads to excessive urination (polyuria)
o Head trauma, tumors, inflammatory disorders of the hypothalamus and pituitary, and surgical complications
o Can also arise spontaneously
o Large volumes of dilute urine with a lower than normal specific gravity
o ↑ Serum sodium and osmolality due to excessive renal loss of free water
o Thirst and polydipsia
o Diabetes insipidus from ADH deficiency is designated as central to differentiate it from nephrogenic diabetes insipidus, which is a result of renal tubular
unresponsiveness to circulating ADH
o Ex. A 42-year-old man has had polyuria and polydipsia for the past 4 months. His medical history shows that he fell off a ladder and hit his head just before
the onset of these problems. On physical examination, there are no specific findings. Laboratory findings include serum Na+, 155 mmol/L; K+, 3.9 mmol/L; Cl–,
111 mmol/L; CO2, 27 mmol/L; glucose, 84 mg/ dL; creatinine, 1 mg/dL; and osmolality, 350 mOsm/mL. The urine specific gravity is 1.002. This patient is most
likely to have a deficiency of which of the following hormones? Vasopressin
 Diabetes insipidus ensues from lack of antidiuretic hormone (ADH), also called arginine vasopressin. There is failure of resorption of free water in
the renal collecting tubules—hence the increased dilute urine with higher serum osmolality and hypernatremia.
- Central (Neurogenic) Diabetes Insipidus
o Hyposecretion of ADH ( Brain tumor, trauma or surgery causing damage)
 Decrease in renal water reabsorption, polyuria up to 18 L/day (normal 1-3 L), frequent day and night time urination
 Inability to produce concentrated urine
 Stimulation of thirst with water intake
o Treatment: replacement therapy with ADH /long-acting analogues
o Ex. A 25-year-old man presents with 3 months of polyuria and increased thirst. The patient suffered trauma to the base of the skull in a motorcycle accident 4
months ago. A 24-hour urine collection shows polyuria but no evidence of hematuria, glucosuria, or proteinuria. The pathogenesis of polyuria in this patient is
most likely caused by a lesion in which of the following areas of the brain? Neurohypophysis
- Nephrogenic Diabetes Insipidus
o Failure of renal response to ADH – defective receptors and/or kidney damage
o Increased ADH plasma level (due to stimulatory effect of increased plasma osmolarity)
o Treatment:
 Restricted salt in diet
 Diuretics which indirectly increase water reabsorption in the kidneys
o Typical historical picture of a dehydrated and malnourished infant with nephrogenic diabetes insipidus (A), looking healthy after rehydration and improved
nutrition(B)
o Antidiuretic action of thiazides in diabetes insipidus is secondary to increased renal sodium excretion. This sodium loss causes extracellular volume
contraction, resulting in reduced GFR and increased sodium and water reabsorption at the proximal tubule. Hence, less sodium and water are delivered to the
distal tubule and collecting duct and less of these are lost in urine, the antidiuretic effect.
- Syndrome of Inappropriate ADH secretion
o ADH excess causes resorption of excessive amounts of free water
 Secretion of ectopic ADH by malignant neoplasms (small-cell carcinoma of the lung)
 Drugs that increase ADH secretion
 CNS infections and trauma
o Hyponatremia, cerebral edema, and resultant neurologic dysfunction
o Although total body water is increased, blood volume remains normal, and peripheral edema does not develop
o Ex. A 60-year-old man with small cell carcinoma of the lung is rushed to the emergency room in a coma after suffering a clonic-tonic seizure. The patient’s
temperature is 37°C (98.6°F), blood pressure 100/50 mm Hg, and pulse 88 per minute. Laboratory studies show a serum sodium of 103 mmol/L, normal serum
levels of BUN and creatinine, and a dilute but otherwise normal urine. A CT scan of the head is normal. Which of the following is the most likely cause of
seizures in this patient? Syndrome of inappropriate ADH secretion
- Syndrome of Inappropriate ADH Secretion (SIADH)
o Decreased urine output with increase in urine osmolality
o Physiological basis of treatment
 Water restriction, infusion of hypertonic NaCl solutions, hypotonic diuresis (drugs that inhibit ADH action – Demeclocycline, Vaptans)
o Decrease in plasma osmolality to the level below 250 mOsm/kg causes brain edema – headache, nausea, lethargy, convulsions, & coma
o Ex. A 69-year-old man has become progressively obtunded over the past week. He has an 80 pack-year history of smoking cigarettes. On physical
examination, he is afebrile and normotensive. A head CT scan shows no intracerebral hemorrhages. Laboratory findings include serum Na+ of 115 mmol/L, K+
of 4.2 mmol/L, Cl– of 85 mmol/L, and bicarbonate of 23 mmol/L. The serum glucose is 80 mg/dL, urea nitrogen is 19 mg/dL, and creatinine is 1.7 mg/dL.
Which of the following neoplasms is most likely to be present in this man? Small cell lung carcinoma
 The syndrome of inappropriate antidiuretic hormone (SIADH) secretion results in increased free water resorption by the kidney and subsequent
hyponatremia. SIADH is most often a paraneoplastic effect, and small cell (oat cell) anaplastic carcinoma of the lung (of neuroendocrine derivation
and seen almost exclusively in smokers) is the most likely
candidate among probable malignant neoplasms.

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