Hypothalamic & Pituitary Dysfunction Flashcards Preview

DEMS: Unit III > Hypothalamic & Pituitary Dysfunction > Flashcards

Flashcards in Hypothalamic & Pituitary Dysfunction Deck (38):
1

Clinical features of GH excess

  • Gigantism → before epiphyseal plate closure
  • Acromegaly → after epiphyseal plate closure
    • acral/facial changes

    • heachaches

    • hyperhydrosis (increased sweating),

    • oligo/amenorrhea

    • obstructive sleep apnea

    • hypertention

    • dyslipidemia

    • paresthesias/carpal tunnel syndrome

    • impaired glucose tolerance/diabetes mellitus


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Dx of GH excess

  • Clinical Features of GH excess AND
  • Elevated IGF-1 level (age and gender matched)-best screening test
    • GH levels fluctuate widely over 24 hrs and normal values can overlap with GH-secreting tumors
  • Confirmatory testing for equivocal IGF-1 level → Oral glucose tolerance test        
  • Pituitary MRI-macroadenomas are detected in most cases of acromegaly (>80%).

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Clinical Presentation of GH deficiency

  • altered body composition (e.g., ↑ central obesity, ↓ lean body mass)
  • ↓ bone mineral density
  • pro-atherogenic lipid profile / ↑  inflammatory markers (e.g., CRP, hypertriglycerides, IL-6)
  • impaired psychological well-being (e.g., fatigue and depression).  

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Dx of GH Deficiency

  • Low IGF-1 in the setting of multiple other pituitary hormone deficiencies
  • Provocative testing for GH reserve:
    • Insulin induced hypoglycemia is gold standard
    • Contraindications: elderly, h/o seizure disorder, coronary artery disease or cerebrovascular disease.
  • GHRH-Arginine is second best test but no longer available in U.S
  • Arginine and glucagon test, but problematic.

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Tx of GH deficiency

Tx → controversial in adults b/c cost/benefit; thus limit to severe GH deficiencies

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Clinical presentation of hyperrolactinemia

  • Hormone Effects-Galactorrhea;
    • causes irregular menses and amenorrhea (♀)
    • erectile dysfunction (♂)
    • infertility, osteoporosis, ↓ libido
  • Female usually microadenoma, male macro (Female:Male = 10:1)
  • Mass Effects if macroadenoma-related (♂ > ♀)  and includes:
    • headaches
    • vision disturbances
    • cranial nerve palsies
    • pituitary hormone deficiencies

 

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Dx of hyperprolactinemia

  • Random PRL level should use gender-based normative ranges
  • Levels usually >100-150 ng/mL with prolactinomas
  • Pituitary MRI

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Clinical presentation fo prolactin deficiency

  • Usually caused by severe lactotrope destruction from any cause
  • Failed lactation in post-partum females, no effect in males.

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Dx of prolactin deficiency

  • Low random basal PRL level

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Clinical presentation of hypercortisolism

  • Specific features of Cushing’s include:
    • facial plethora
    • easy bruising
    • wide (>1 cm) violaceous striae
    • proximal muscle weakness
  • General signs/symptoms (poor specificity):
    • weight gain/obesity, diabetes, hypertension, irregular menses, dorsocervical hump, acne, low libido, depression or hirsutism
  • Most Often iatrogenic, i.e. chronic steroid use
  • Rare → 3 / 1 million

 

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Screening for hypercortisolism

  • Disrupted Circadian Rhythm → midnight salivary or serum cortisol
  • Increased  Filtered Cortisol Load → 24 hour urinary cortisol
  • Attenuated Negative Feedback → 1 mg dexamethasone suppression test (1 mg dexamethasone given at 11-12 p.m., followed by ~8 am cortisol level. Normal cortisol suppression <1.8 ug/dl)

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Dx of hypercortisolism

  • plasma ACTH level
  • imaging
  •  inferior petrosal sinus sampling
  • Caveat: “Pseudo-Cushing’s” disease:
    • non-tumoral activation of hypothalamic-pituitary-adrenal (HPA) axis (e.g., severe depression, alcoholism, marked stressors) ==> false-positive screening 

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Clinical presentation of cortisol deficiency

  • Fatigue, pallor
  • anorexia, weight loss
  • nausea, vomiting, abdominal pain,  
  • hyponatremia
  • hypoglycemia
  • orthostatic dizziness
  • scant axillary/pubic hair which is DHEA-S dependent.  

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Dx of cortisol deficiency

  • Random a.m. cortisol level
    • <3 ug/dl = confirmatory
    • >18 = excludes
  • Stimulation tests to assess HPA axis
    • Insulin-induced hypoglycemia (gold standard) 
      • hard to administer = ↑ resources
    • Cosyntropin (synthetic ACTH 1-24) stimulation test
      • valid for assessing HPA axis only if prolonged (several weeks-months) interruption of pituitary signaling.

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Clinical presentation of LH/FSH Tumor in Females

  • Hypogonadotropic Hypogonadism
  • Most often clinically silent.
  • Females:
    • anovulatory cycles
    • oligo/amenorrhea
    • infertility
    • hot flashes
    • vaginal dryness/atrophy
    • dyspareunia
    • reduced bone mineral density (BMD)

 

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Clinical presentation of LH/FSH Tumor in Males

  • Hypogonadotropic Hypogonadism
  • Most often clinically silent.
  • Males: Reduced libido, erectile dysfunction, oligospermia or azoospermia, testicular atrophy, infertility, decreased muscle mass and low BMD.

 

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Rare presentation of LH/FSH tumor

  • Rare presentation (from functionally-intact FSH/LH molecules) include:
    • ovarian hyperstimulation syndrome (females)
    • macro-orchidism (males).

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Dx of LH/FSH tumor

1. Clinical

2. Blood work: FSH/LH, T and E2, alpha-subunit

3. Imaging: Pituitary MRI

4. Immunohistochemical analyses (+FSH or LH staining of the resected tumor) establishes the diagnosis

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Clinical presentation of Thyrotropinoma

  • Thyrotropinoma (TSHoma)-similar clinical presentation to primary hyperthyroidism
  • hyperthyroid sx = goitre, tremor, weight loss, heat intolerance, hair loss, diarrhea, irregular menses  AND
  • mass effects (i.e., headaches, vision loss) from macroadenoma

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Dx of Thyrotropinoma

  • Elevations of free thyroxine (T4) and triiodothyronine (T3) concentrations
  • non-suppressed (inappropriately normal or frankly elevated) TSH level.
  • Pituitary MRI

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Clinical presentation of Central hypothyroidism

  • Central Hypothyroidism-similar clinical presentation to primary hypothyroidism
  • fatigue
  • weight gain
  • cold intolerance
  • constipation
  • hair loss
  • irregular menses

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Dx of central hypothyroidism

  • Central hypothyroidism: Low Free T4 levels in the setting of a low or normal TSH.
  • Pituitary MRI  

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Clinical presentation of SIADH

  • Presentation depends on the severity and rate of hyponatremia development
  • Manifests with neurological symptoms from osmotic fluid shifts and brain edema
  • Symptoms range from mild →  severe, and include: headaches, fatigue, anorexia, nausea, vomiting, altered sensorium, seizure, coma and death

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Dx of SIADH

  • Hyponatremia → Na+ < 135 mEq/L (very common) and hypotonic plasma → osmolality < 275 mOsm/kg
  • Inappropriate urine concentration (Urine Osm >100 mOSm/kg) with normal renal function
  • Euvolemic Status → No pitting edema, no JVD
  • Elevated urinary sodium excretion (with normal salt and water intake)

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Clinical presentation of Diabetes Insipidus (central or nephrogenic)

  • Polyuria/Nocturia, Polydipsia
  • Hypernatremia quickly develops if the patient does not have an intact thirst mechanism (e.g., adipsia from hypothalamic injury), or has limited access to water (such as in the elderly).

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Dx of Diabetes Insipidus (central or nephrogenic)

  • Confirm polyuria with a 24 hr urine volume collection (normalize to a 24 hr creatinine)
  • Assess plasma osmolality and urine osmolality
  • Water Deprivation Test
  • Pituitary Imaging (for suspected neurogenic DI)

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Conditions necc. to exclude with polyuria for dx of DI

  • Exclude: Primary polydipsia (psychogenic), Pregnancy (increased ADH metabolism)
  • Exclude hyperglycemia, renal insufficiency and electrolyte disturbances (K+, Ca2+).

 

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Clinical Presentation of hypopituitarism

  • Depends on the severity of the pituitary hormone deficiencies and their rate of development.
  • Represents a continuum from partial to complete pituitary hormone deficiency.
  • Similar presentation to target gland hormone deficiency as detailed above with some exceptions (e.g., primary adrenal insufficiency also presents w/hyperkalemia from mineralcorticoid deficiency and hyperpigmentation from ACTH excess)

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Dx of hypopituitarism

  • Assessment of pituitary hormones and target hormones as previously detailed for basal and provocative testing.
  • Treat with end organ hormone replacement.

 

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Major fxns of posterior pituitary

  • Neurohypophysis-20% of the pituitary gland - makes ADH and Oxytocin
  • AVP = arginine vasopressin = ADH = antidiuretic hormone
  • Oxytocin-mediates milk let-down and uterine contractions

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Stimulation leading to AVP/ADH release + downstream effects

  • AVP release is stimulated by:
    • High osmolar states (via hypothalamic osmoreceptors)
    • Hypovolemia (via baroreceptors)
  • AVP causes free water retention (via V2 receptors in the kidney) and vasoconstriction (via V1 receptors of blood vessels)

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Most common posterior pituitary disorders

  • SIADH = sydrome of inappropriate ADH
    • → inappropriate concentration of urine excreted in the setting of hypo-osmolality and hyponatremia
  • Diabetes insipidus ==> a syndrome of hypotonic polyuria as a result of either

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General characteristics of SIADH

  • SIADH → inappropriate concentration of urine excreted in the setting of hypo-osmolality and hyponatremia.
  • One of the most common causes of hyponatremia
  • Etiologies → Malignancy, pulmonary disorder, CNS disorder, Drugs, Other (nausea, stress, pain)
  • Clinical presentation (see separate card)
  • Diagnosis (see separate card)

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General characteristics of Diabetes Insipidus

  • a syndrome of hypotonic polyuria as a result of either:
  • Inadequate ADH secretion
  • Inadequate renal response to ADH
  • Hallmark → Voluminous (Urine output > 40 ml/kg/day) dilute urine
  • Causes → Central diabetes insipidus, nephrogenic diabetes insipidus, pregnancy-increased ADH metabolism from placental vasopressinase, psychogenic polydipsia

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Etiology of hypopituitarism

  • Pituitary tumors and/or their treatment (75% of cases)
  • parasellar tumors (e.g., craniopharyngiomas, meningiomas), pituitary infarction/apoplexy/Sheehan’s syndrome
  • infiltrative diseases (sarcoidosis, lymphocytic hypophysitis, hemochromatosis, Langerhan’s cell histiocytosis)
  • infection (TB, abscess)
  • traumatic brain injury/subarachnoid hemorrhage
  • genetic defects

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Order of pituitary hormone deficiencies in hypopituitarism

  • Generally predictable order of pituitary hormones deficiencies:
  • GH≈FSH/LH > TSH ≈ACTH > PRL
  • ADH deficiency- infrequent with pituitary adenomas, but common with metastatic diseases to the pituitary gland (e.g., lung, breast or colon) and craniopharyngiomas.

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Tx of hypopituitarism

  • Glucocorticoids- Prednisone or hydrocortisone–first line therapies.
  • Thyroid hormone-multiple T4 formulations available.
  • Testosterone or estrogen
  • Various formulations-oral/transdermal E2, transdermal/IM Testosterone
  • Gonadotropin therapy is sometimes required for fertility treatment.
  • Growth hormone-subcutaneous shots (controversial use in adults regarding cost-to- benefit ratio).
  • dDAVP-oral or nasal formulations
  • PRL- SQ formulation, research use only.

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