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22 - Endocrine Disorders

Terms in this set (16)

I. Overview of Endocrine Disorders:
NEGATIVE FEEDBACK LOOPS
NEGATIVE FEEDBACK LOOPS - control an increase or decrease in hormone product

Example: Increased Ca++ decreases parathyroid hormone (PTH); Decreased Ca++ increases PTH
I. Overview of Endocrine Disorders: STIMULATION TESTS
STIMULATION TESTS - evaluate Hypofunctioning disorders

Example: ACTH stimulation test is used in the workup of Hypocortisolism

CAUSES OF HYPOFUNCTION:
1) Autoimmune Destruction:
- Addison's Dx
- Hashimoto's Thyroiditis
** Most common cause of Endocrine gland hypofunction is Autoimmune Dx


2) Infarction:
- Sheehan's Postpartum Necrosis
- Waterhouse-Friderichsen Syndrome

3) Decreased H'mone Stimulation:
- decreased TSH in Hypopituitarism

4) Enzyme deficiency, infection, neoplasia, congenital disorder
I. Overview of Endocrine Disorders:
SUPPRESSION TESTS
SUPPRESSION TESTS - evaluate HYPERfunctioning disorders

Example: Dexamethasone Suppression Test evaluates Hypercortisolism

Most hyperfunctioning disorders can NOT be suppressed
** Exceptions are Prolactinoma & Pituitary Cushing syndrome

CAUSES OF HYPERFUNCTION:
1) Adenoma
2) Acute Inflammation
3) Hyperplasia
4) Cancer
II. Hypothalamus Disorders:
TUMORS altering Hypothalamic Function
TUMORS ALTERING HYPOTHALAMIC FUNCTION:
** Most common cause of endocrine gland Hyperfunction is Benign Adenoma

1) Pituitary Adenoma
** Most common tumor affecting the Hypothalamus
2) Craniopharyngioma
3) Midline hamartoma (Not a neoplasm)
4) Langerhans histiocytosis
II. Hypothalamus Disorders:
INFLAMMATORY DISORDERS altering Hypothalamic Function
INFLAMMATORY DISORDERS altering Hypothalamic Function:

1) SARCOIDOSIS
- produces Granulomatous inflammation
2) MENINGITIS
II. Hypothalamus Disorders:
CLINICAL FINDINGS
CLINICAL FINDINGS of Hypothalamic Dysfunction:

1) SECONDARY HYPOPITUITARISM
- NO releasing hormones to stimulate the Anterior Pituitary
2) CENTRAL DIABETES INSIPIDUS (CDI)
- ADH is synthesized in the hypothalamus
3) HYPERPROLACTINEMIA
- loss of Dopamine inhibition causes galactorrhea
4) PRECOCIOUS PUBERTY
- Most common cause in boys is a Midline Hamartoma
5) VISUAL FIELD DISTRUBANCES
- usually Bitemporal Hemianopia (XO I OX)
6) MASS EFFECTS
- produces Obstructive Hydrocephalus
7) GROWTH DISORDERS
- Dwarfism in children
8) KALLMANN'S SYNDROME
- AD mutation; maldevelopment of the Olfactory Bulbs & GnRH-producing cells; presents w/ delayed puberty, Anosmia, & color blindness; Lab findings include Decreased FSH, LH, testosterone, and sperm count

""True" Precocious-Puberty implies a CNS origin for the disorder, but Pseudo-Precocious puberty implies a peripheral cause (e.g., adrenogenital syndrome). True precocious puberty in boys is the onset of puberty before 9 years of age. The most common cause is a midline hamartoma in the hypothalamus. True precocious puberty in girls is the onset of puberty before 8 years of age. In most cases, it is idiopathic and less likely to be caused by a midline hamartoma."
- Precocious Puberty: True if CNS origin, Pseudo if peripheral cause
III. Pineal Gland Disorders:
CLINICAL ANATOMY
CLINICAL ANATOMY:

1) Midline location above the Quadrigeminal Plate
2) Site for melatonin production
- Superior Cervical Sympathetic Ganglia stimulates receptors on Pinealocytes -> causes release of Melatonin into spinal fluid and blood

MELATONIN:
1) important in sleep/moods and circadian rhythms
released @ night
2) used in the tx of sleep & mood disorders
III. Pineal Gland Disorders:
PINEAL DISORDERS
PINEAL DISORDERS:

1) DYSTROPHIC CALCIFICATION:
- begins in childhood; approx 80% are calcified in 70-80 y/o
- useful in showing shifts due to Mass Lesions in the brain

2) PINEAL TUMORS:
- majority are Germ Cell tumors resembling seminomas
-minority of tumors are Teratomas
III. Pineal Gland Disorders:
CLINICAL FINDINGS
CLINICAL FINDINGS:

1) VISUAL DISTURBANCES:
- paralysis of upward conjugate gaze (ie. Parinaud's syndrome; "setting sun" sign)

2) OBSTRUCTIVE HYDROCEPHALUS:
- due to compression of the Aqueduct of Sylvius in the 3rd ventricle

"Hydrocephalus & Parinaud's syndrome. Note the increased head circumference & paralysis of upward gaze in this newborn with stenosis of the aqueduct of Sylvius."
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Epidemiology)
ANTERIOR PITUITARY HYPOFUNCTION:

Rathke's Pouch is an ectodermal derivative derived from the oral cavity
- it develops into the anterior lobe of the Pituitary Gland

EPIDEMIOLOGY:
1) Partial or complete loss of secretion of one or more hormones
- Infarctions of the pituitary invariably lead to panhypopituitarism
2) Increased incidence of vascular or cerebrovascular disease
3) Types of pituitary dysfunction:
a) PRIMARY HYPOPITUITARISM (ie. Pituitary Dysfunction) - approx 75% of the gland must be destroyed
b) SECONDARY HYPOPITUITARISM (ie. Hypothalamic Dysfunction) - decreased hypothalamic releasing factors
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Causes of Hypopituitarism (1&2))
CAUSES OF HYPOPITUITARISM:

1) NON-FUNCTIONING (Null) PITUITARY ADENOMA:
** Most common cause of Hypopituitarism in adults
- microadenoma < 10 mm; macroadenoma > 10 mm
- assoc w/ Multiple Endocrine Neoplasia (MEN-1) syndrome (MEN-1 = pituitary adenoma, hyperparathyroidism, pancreatic tumor (Zollinger-Ellison syndrome or Insulinoma))

2) CRANIOPHARYNGIOMA:
** Most common cause of Hypopituitarism in children
- BENIGN pituitary tumor derived from Rathke's pouch remnants
- located above the Sella Turcica -> extends into Sella Turcica & destroys the gland
- Cystic tumor w/ hemorrhage & calcification
- Commonly causes Bitemporal Hemianopia (XO I OX)
- may produce Central Diabetes Insipidus (CDI)
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Causes of Hypopituitarism (3-6))
CAUSES OF HYPOPITUITARISM:

3) SHEEHAN'S POSTPARTUM NECROSIS:
- Hypovolemic shock (blood loss) causes infarction (ie. pituitary infarction secondary to shock
- sudden cessation of lactation due to loss of prolactin -> eventual development of Hypopituitarism

4) PITUITARY APOPLEXY:
- term "apoplexy" refers to a sudden onset of neurologic dysfunction
- Most often due to Hemorrhage/Infarction of pre-existing Pituitary Adenoma
- predisposing factors include: Trauma, Pregnancy (Sheehan's Postpartum Necrosis, a non-tumorous cause), & tx of a Prolactinoma w/ Bromocriptine
- Clinical findings: sudden onset of HA, mental status dysfunction, visual disturbances, & H'mone dysfunction

5) SICKLE CELL ANEMIA:
- Pituitary infarction from vascular occlusion by irreversibly sickled cells

6) LYMPHOCYTIC HYPOPHYSITIS:
- Female-dominant autoimmune destruction of the pituitary gland
- occurs during or after pregnancy
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Causes of Hypopituitarism (7&8))
CAUSES OF HYPOPITUITARISM:

7) EMPTY SELLA SYNDROME:
- Epidemiology: radiologic studies show an empty sella turcica; Primary & Secondary types
a) PRIMARY TYPE - anatomic defect above pituitary; subarachnoid space extends into sella turcica & fills up w/ CSF; Increase in pressure on the pituitary gland causes it to flatten out; assoc w/ Women who are obese & have high blood pressure
b) SECONDARY TYPE - regression in size due to radiation, trauma, surgery

8) HYPOTHALAMIC DYSFUNCTION:
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Clinical & laboratory findings of Pituitary TROPHIC HORMONE DEFICIENCIES (1&2))
Clinical and laboratory findings of Pituitary TROPHIC HORMONE DEFICIENCIES:

1) GONADOTROPINS (FSH & LH):
- children have delayed puberty
- adult females have Secondary Amenorrhea; produces osteoporosis, hot flashes (lack of Estrogen), decreased libido
- males have impotence, due to decreased libido from decreased Testosterone
**** GnRH stimulation test:
- No significant increase of FSH/LH in hypopituitarism
- Eventual increase of FSH/LH in hypothalamic disease
**** Metyrapone test:
- stimulation test of pituitary ACTH reserve
- metyrapone inhibits adrenal 11-hydroxylase, which causes a decrease in cortisol & a corresponding increase in plasma ACTH (pituitary) and 11-deoxycortisol (adrenal), which is proximal to the enzyme block
- in Hypopituitarism, neither ACTH or 11-deoxycortisol are increased

2) GROWTH H'MONE (GH):
- decreased GH decreases synthesis & release of IGF-1
- children have growth delay: delayed fusion of epiphyses; bone growth does not match the age of the child
- adults have hypoglycemia: decreased gluconeogenesis; loss of muscle mass; increased adipose around waist
**** Arginine & Sleep Stimulation tests:
- NO increase in GH or IGF-1; normally, GH & IGF-1 are released @ 5am
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Clinical & laboratory findings of Pituitary TROPHIC HORMONE DEFICIENCIES (3&4))
Clinical and laboratory findings of Pituitary TROPHIC HORMONE DEFICIENCIES:

3) THYROID-STIMULATING H'MONE (TSH):
- Secondary hypothyroidism: decreased serum T4 and TSH
- cold intolerance, constipation, weakness
- NO increase in TSH after TRF stimulation

4) ADRENOCORTICOTROPIC H'MONE (ACTH):
**** Metyrapone test:
- stimulation test of pituitary ACTH & adrenal gland reserve
- Metyrapone inhibits adrenal 11-hydroxylase, which causes a decrease in cortisol & a corresponding increase in plasma ACTH (pituitary) and 11-deoxycortisol (adrenal), which is proximal to the enzyme block
- in hypopituitarism, neither ACTH or 11-deoxycortisol are increased; in adrenal disease, ACTH is increased, but 11-deoxycortisol is decreased
IV. Pituitary Gland Disorders:
ANTERIOR PITUITARY HYPOFUNCTION (Diagnosis & Treatment)
ANTERIOR PITUITARY HYPOFUNCTION

DIAGNOSIS:
1) MRI (better test) or CT of Sella Turcica
2) Stimulation tests for the various deficiencies

TREATMENT:
1) Surgery for tumors (usually transsphenoidal)
2) Hormone replacement for deficiencies
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