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Flashcards in Hypothalamic & Pituitary Dysfunction Deck (38)
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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


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%).


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).  


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.


Tx of GH deficiency

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


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



Dx of hyperprolactinemia

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


Clinical presentation fo prolactin deficiency

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


Dx of prolactin deficiency

  • Low random basal PRL level


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



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)


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 


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.  


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.


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)



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.



Rare presentation of LH/FSH tumor

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


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


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


Dx of Thyrotropinoma

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


Clinical presentation of Central hypothyroidism

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


Dx of central hypothyroidism

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


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



  • 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)


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).


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)


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+).



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)


Dx of hypopituitarism

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



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