Pituitary Dysfunction Flashcards
What are the stimulatory and inhibitory factors of Growth Hormone?
Stimulatory:
Sleep, stress, Ghrelin, Protein/Arginine, Hypoglycemia
Inhibitory:
Obesity/FFA, Glucocorticoids, Leptin, Hyperglycemia
What are the signs of excess or deficiency of growth hormone?
Excess: Acromegaly
Deficiency: GH Deficiency
What are the signs of excess or deficiency of PRL?
Excess: Hypogonadism
Deficiency: Failed Lactation
What are the signs of excess or deficiency of FSH/LH?
Excess: rarely clinically evident
Deficiency: Hypogonadism
What are the signs of excess or deficiency of ACTH?
Excess: Cushing’s disease
Deficiency: Adrenal Insufficiency
What are the signs of excess or deficiency of TSH?
Excess: Hyperthyroidism
Deficiency: Hypothyroidism
What are the signs of excess or deficiency of ADH?
Excess: SIADH
Deficiency: Diabetes Insipidus
What distinguishes primary gland failure from secondary or tertiary causes?
Levels of pituitary/tropic hormones present. Low target gland or tissue function in the presence of high stimulatory hormones indicates a primary gland failure. Low target gland or tissue function in the presence of low stimulatory hormones indicates secondary or tertiary gland failure.
What dynamic test is used to detect excess GH/acromegaly and what are the diagnostic criteria?
Oral glucose test. Administration of oral glucose (75mg) should depress secretion of GH due to insulin feedback. Continued expression of GH indicates GH excess.
Old pictures for comparison of physical features, elevated IGF-1 levels over 24 hrs.
What are the treatments for GH excess/acromegaly?
Surgery
Medical therapies: somatostatin analogs, Growth Hormone Receptor Antagonist
Radiation Therapy
What are the manifestations of growth hormone deficiency?
Body composition: Inc fat, dec muscle mass and exercise capacity
Bone strength: Inc bone loss and fracture risk
Metabolic/Cardovascular: Inc cholesterol, Inc inflammatory and reactive markers (C RP)
Psychological Wellbeing: Impaired energy and mood, QoL
What are the tests for diagnosis and treatments for growth hormone deficiency?
Tests: Insulin induced hypoglycemia, Low IGF-1 level in setting of other pituitary hormone deficiency
Treatment:
GH replacement therapy.
Approved in children
Controversial in adults due to cost/benefit ratio
What are the normal PRL levels and what are physiologic, pathologic, and pharmacologic causes of hyperprolactinemia?
PRL Levels norm
What are the signs/symptoms of prolactinomas in men and women and what is the diagnostic criteria?
Men: Headache, impotence, anterior pituitary malfunction, EOM paralysis, visual field abnormalities, galactorrhea
Women: Galactorrhea, Menstrual irregularities, infertility, Impaired GnRH pulsatility
Diagnosis: PRL levels >150g/dl, Pituitary MRI
What is the etiology, presentation, and diagnostic criteria of PRL deficiency
Etiology: Severe pituitary destruction from any cause (tumors, infiltrative or infectious disease, infarction, radiation)
Presentation: Failed lactation in post-partum women, no known effect in males
Diagnosis: Low basal PRL level
What are the primary functions of cortisol and what are signs of cortisol excess?
Gluconeogenesis, Breakdown of fat and protein for glucose production, Control inflammatory reactions
Changes in macronutrient metabolism (central obesity, moon facies, osteoporosis, diabetes, hypertriglyceridemia)
Changes in sex hormones (amenorrhea, infertility, hair growth in women, impotence)
Salt and water retention (HTN, edema)
Impaired immunity
Neurocognitive changes
What is Cushing’s disease and what are specific signs?
Corticotrope adenoma resulting in increased ACTH -> cortisol excess
Moon facies, Wide violaceous striae, Spontaneous ecchymoses (bruising), Proximal muscle weakness, Early/atypical osteoporosis
What are the screening tests for Cushing’s Syndrome?
Disrupted Circadian Rhythm:
Midnight Salivary or Serum Cortisol
Increased Filtered Cortisol Load:
24 hr Urine Free Cortisol
Attenuated Negative Feedback: Low Dose (1 mg) Dexamethasone Suppression test (11-12 p.m.)
What are the symptoms of adrenal insufficiency and the secondary/teritary causes?
Fatigue Anorexia, nausea/vomiting, weight loss Generalized malaise/aches Scant axially/pubic hair Hyponatremia/hypoglycemia
Suppression of HPA axis (tumor resection, glucocorticoid use, opioid or megace use
Hypothalamus/pituitary disease or treatments
Isolated ACTH deficiency (very rare)
What are the basal tests for adrenal insufficiency?
Random a.m. cortisol level, 18 ug/dl (excludes AI diagnosis)
additional provocative testing required for equivocal results.
What are the two forms of hypogonadism?
Hypergonadotropic hypogonadism: High GSH and LH
Hypogonadotropic hypogonadism: Low GSH and LH
What are the clinical features of hypogonadism in men and women?
Men: Reduced libido, erectile dysfunction, oligo- or azospermia, infertility, dec muscle mass, dec bone mineral density, possible hot flashes
Women: Oligomenorrhea or amenorrhea, vaginal dryness, hot flashes, decreased libido, breast atrophy, dec bone mineral density
What are the clinical presentation and diagnosis of central hyperthyroidism?
Clinical Presentation:
Thyrotropinoma (TSHoma)-similar clinical presentation to primary hyperthyroidism (i.e., goitre, tremor, weight loss, heat intolerance, hair loss, diarrhea, irregular menses) but also with associated mass effects (i.e., headaches, vision loss, loss of pituitary gland function) from macroadenoma.
Diagnosis:
Elevated Free T4 and a non-suppressed TSH
Pituitary MRI (>80% macroadenomas)
What are the etiologies, presentation and diagnosis of central TSH deficiency?
Etiologies:
Pituitary/Hypothalamic Diseases and/or their treatments
Critical Illness/Starvation-Euthyroid Sick Syndrome
Congenital defects (TSH-beta mutations, PROP1, POUF1 mutations)
Drug induced-supraphysiologic steroids, dopamine, retinoids.
Clinical presentation:
similar to primary hypothyroidism (e.g., fatigue, weight gain, cold intolerance, constipation, hair loss, irregular menses). Possible mass effects
Diagnosis: Low Free T4 levels in the setting of a low or normal TSH.
What is the definition and etiologies of hypopituitarism?
Definition: Deficiency of 1 or more pituitary hormones. Panhypopituitarism=loss of all pituitary hormones
Etiologies:
Congenital-Genetic Diseases (transcription factor mutations)
Acquired-Pituitary Lesions and/or their treatments (75%):
- Macroadenomas/Pituitary Surgery/Radiation Therapy
- Infiltrative/Infectious/Granulomatous diseases
- Traumatic Brain Injury/Subarchnoid Hemorrhage
- Apoplexy
How is hypopituitarism managed?
Specific to the hormones lacking as a result. Treatment of Anterior Pit. Hormone Deficiencies (End Organ Hormone Replacement):
Thyroid – Multiple L-thyroxine formulations available.
Adrenal – Physiologic hydrocortisone or prednisone
- Medic Alert Bracelet, Sick day rules for glucocorticoid replacement
- No mineralcorticoid replacement needed
Gonadal –
- Various formulations-oral/transdermal E2, transdermal/IM Testosterone
- Gonadotropin or pulsatile GnRH therapy
Growth Hormone
- Various Formulations of subcutaneous shots (not orally active).
What is the mechanism of ADH-regulated antidiuretic effects in the kidneys?
ADH binds to V2 receptors in the kidney increasing cAMP which increases the production and expression of aquaporin-2 water channels on the apical membrane.
What is the definition and hallmark finding in SIADH?
Definition: A syndrome of inappropriate AVP release/action in the absence of physiologic osmotic or hypovolemic stimulus.
Hallmark finding is the excretion of inappropriately concentrated urine in the setting of hypo-osmolality and hyponatremia.
SIADH is one of the most frequent causes of hyponatremia, and occurs in an estimated:
15-22% of hospitalized patients
5-7% of ambulatory patients
What are the etiologies of SIADH?
Malignant Disease- Carcinoma, Lymphoma, Sarcomas
Pulmonary Disorders-Infections, Asthma, Cystic Fibrosis, Positive Pressure Ventilation
CNS Disorders-Infection, Tumors, Trauma, Bleeds
Drugs-Stimulate/Potentiate AVP release/actions
Narcotics, Nicotine, Anti-psychotics, Carbamazepine, Vincristine
Misc.-Nausea, Stress and Pain
What is the diagnosis and treatment of SIADH?
Criteria:
Hyponatremia (Na+ 100 mOSm/kg) with normal renal function
Euvolemic Status (no orthostatics hypotension)
Exclusion of other potential causes of euvolemic hypo-osmolality
Hypothyroidism
Hypocortisolism
Treatment:
Identify and Reverse Underlying Disorder (when possible)
Treatment depends on the severity of hyponatremia, the rate of development and the patient’s symptomatology
Mild-to-Moderate Hyponatremia (Na+ ~120-134 mmol/L)
Water Restriction (500-1000L/24hrs)
V2 Receptor Antagonists ($$$)
Salt tablets, Lasix, Urea (Europe)
Severe Hyponatremia (usually Na+
What is the definition, hallmark finding, and general causes of Diabetes Insipidus?
Definition-DI is a syndrome of hypotonic polyuria as a result of either:
Inadequate ADH secretion
Inadequate renal response to ADH
Hallmark-Voluminous (Urine output > 40ml/kg/d) dilute urine
Main Causes: Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Pregnancy-increased ADH metabolism from placental vasopressinase, but is generally not clinically relevant. Psychogenic Polydipsia
Clinical Significance: Can lead to severe dehydration if thirst mechanisms are impaired, or if the patient has limited access to water.
What are the etiologies of nephrogenic DI?
Nephrogenic DI
Congenital: X-linked recessive AVP V2 receptor gene mutation; autosomal recessive aquaporin-2 water channel gene mutation
Drugs: demeclocycline, lithium, amphotericin B
Electrolyte abnormalities: hypokalemia and hypercalcemia
Infiltrative kidney diseases: sarcoidosis and amyloidosis
Vascular disease: sickle cell anemia
What are the etiologies of neurogenic DI?
Neurogenic DI
Neoplasms: craniopharyngioma, metastatic pituitary disease (e.g., colon, breast, lung)
Idiopathic:+AVP Ab
Congenital defects: autosomal dominant AVP neurophysin gene mutation
Inflammatory/Infectious/granuloma pituitary diseases: lymphocytic hypophysitis,histiocytosis, sarcoidosis
Trauma/Vascular event: neurosurgery, TBI/deceleration injury
What is the typical course of post-operative or trauma related DI?
Classic Triphasic Response:
1° phase– DI-polyuric phase due to axonal shock/decreased AVP release (days 1-5)
2° phase – SIADH from degenerating neurons/excessive AVP release (days 6-11)
3° phase-Permanent DI after depleted ADH stores and if >80% AVP neuronal cell death
Permanent DI-uncommon complication with an experienced neurosurgeon (
What is the treatment for central DI?
Anti-Diuretic Hormone Replacements
First Line-dDAVP (nasal, oral or parenteral routes of administration)
- Longer half-life than ADH
- No Vasopressor Effect
Second-Line-ADH (IV, SQ or IM routes of administration).
Goals:
Resolution of Polyuria/Polydipsia
- Minimal disruption of sleep/daily routine
Normal Serum Sodium
