Hypothalamic & Pituitary Dysfunction Flashcards
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.
- Insulin-induced hypoglycemia (gold standard)
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
- Clinical
- Blood work: FSH/LH, T and E2, alpha-subunit
- Imaging: Pituitary MRI
- 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
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)