Hypothalamic & Pituitary Dysfunction Flashcards

1
Q

Clinical features of GH excess

A
  • 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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2
Q

Dx of GH excess

A
  • 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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3
Q

Clinical Presentation of GH deficiency

A
  • 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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4
Q

Dx of GH Deficiency

A
  • 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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5
Q

Tx of GH deficiency

A

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

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6
Q

Clinical presentation of hyperrolactinemia

A
  • 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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7
Q

Dx of hyperprolactinemia

A
  • Random PRL level should use gender-based normative ranges
  • Levels usually >100-150 ng/mL with prolactinomas
  • Pituitary MRI
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8
Q

Clinical presentation fo prolactin deficiency

A
  • Usually caused by severe lactotrope destruction from any cause
  • Failed lactation in post-partum females, no effect in males.
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9
Q

Dx of prolactin deficiency

A
  • Low random basal PRL level
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10
Q

Clinical presentation of hypercortisolism

A
  • 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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11
Q

Screening for hypercortisolism

A
  • 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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12
Q

Dx of hypercortisolism

A
  • 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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13
Q

Clinical presentation of cortisol deficiency

A
  • 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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14
Q

Dx of cortisol deficiency

A
  • 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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15
Q

Clinical presentation of LH/FSH Tumor in Females

A
  • 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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16
Q

Clinical presentation of LH/FSH Tumor in Males

A
  • Hypogonadotropic Hypogonadism
  • Most often clinically silent.
  • Males: Reduced libido, erectile dysfunction, oligospermia or azoospermia, testicular atrophy, infertility, decreased muscle mass and low BMD.
17
Q

Rare presentation of LH/FSH tumor

A
  • Rare presentation (from functionally-intact FSH/LH molecules) include:
    • ovarian hyperstimulation syndrome (females)
    • macro-orchidism (males).
18
Q

Dx of LH/FSH tumor

A
  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
19
Q

Clinical presentation of Thyrotropinoma

A
  • 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
20
Q

Dx of Thyrotropinoma

A
  • Elevations of free thyroxine (T4) and triiodothyronine (T3) concentrations
  • non-suppressed (inappropriately normal or frankly elevated) TSH level.
  • Pituitary MRI
21
Q

Clinical presentation of Central hypothyroidism

A
  • Central Hypothyroidism-similar clinical presentation to primary hypothyroidism
  • fatigue
  • weight gain
  • cold intolerance
  • constipation
  • hair loss
  • irregular menses
22
Q

Dx of central hypothyroidism

A
  • Central hypothyroidism: Low Free T4 levels in the setting of a low or normal TSH.
  • Pituitary MRI
23
Q

Clinical presentation of SIADH

A
  • 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
24
Q

Dx of SIADH

A
  • 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)
25
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
31
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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