Pituitary dysfunction Flashcards
GH
- def
- excess
- assay
Acromegaly
GH Deficiency
IGF-1
PRL
- def
- excess
Failed Lactation
Hypogonadism
FSH/LH
- def
- excess
- assay
Hypogonadism
Rarely Clinically Evident
Testosterone estradiol
ACTH
- def
- excess
- assay
Adrenal Insufficiency
Cushing’s Disease
cortisol and DHEA-S
TSH
- def
- excess
- assay
Hypothyroidism
Hyperthyroidism
TSH
free T4
total T3
ADH
- def
- excess
Diabetes Insipidus
SIADH
which hormones can we do dynamic testing on?
Growth hormone
ACTH
Growth hormone
-physiology
stimulator- GHRH
Inhibitor Somatostatin
-acts on liver to produce IGF-1, which feeds back (-) on pituitary and hypothalamus
-pulsatile
Growth hormone excess
- disease
- signs symptoms
- Tx
Gigantism- pre puberty growth hormone excess
Acromegaly- post puberty growth hormone excess
- acral facil achnages
- headaches, hyperhidrosis
- oligo,amenorhea
- obstructive sleep apnea
- HTN, dyslipidemia, paratheisas, carpal runnel
- Impaired glucose tolerance, DM
Tx-Surgery Medical Therapies -Somatostatin Analogs -Growth Hormone Receptor Antagonist Radiation Therapies
Dx of AoGHD
- Provocative Testing for GH Reserve
Limited Reagents
-Insulin induced hypoglycemia (gold standard).
——Contraindications: Elderly, h/o seizure disorder, coronary artery disease or cerebrovascular disease.
-GHRH-Arginine (second best test), although no longer available in U.S
-Available tests: Arginine and glucagon stimulation tests - IGF-1 Level -Low (in the setting of multiple other
pituitary hormone deficiencies). Must be age/gender-matched.
causes of hyperprolactinemia
Physiological
-Pregnancy, suckling, sleep, stress
Pharmacological
-Estrogens (OCPs)
-Antipsychotics, antidepressants (TCAs),
anti-emetics (e.g., Reglan), opiates
Pathological
-Pituitary Stalk Interruption
-Hypothyroidism, chronic renal/liver failure, seizure (cross talk)
-ProlactinomaProlactinoma
- womens manifestations
- mens manifestations
- Dx
women- often present with microadenomas
- galactorhea
- menstrual irregularities
- infertility
- (impairs GnRH pulse generator
Men- macroadenomas
- galactorrhea
- visual field abnormalities
- headache
- impotence
- EOM paralysis
- anterior pituitary malfunction
Diagnosis
-Random PRL level (gender-based normative ranges)
-Levels usually correlate with tumor size
>100-150 ng/dl with microadenomas
>200-250 ng/dl with macroadenomas
Pituitary MRI (with/without contrast)
prolactin deficiency
Etiology: Severe pituitary (lactotrope) destruction from any cause (e.g., pituitary tumors, infiltrative diseases, infectious diseases, infarction, neurosurgery or radiation).
Clinical Presentation: Failed lactation in post-partum females, no known effect in males.
Diagnosis: low basal PRL level
Cortisol Excess (Hypercortisolism)
- ACTH dependent causes
- ACTH independent causes
ACTH-Dependent
- Corticotrope Adenoma (Cushing’s Disease)
- Ectopic Cushing’s (ACTH/CRH tumors)
ACTH-Independent
- Adrenal Adenomas
- Adrenal Carcinoma
- Nodular Hyperplasia (micro or macro)
no specific manifesatiions Cushings Syndrome
Obesity Fatigue Menstrual Irregularities Hirsutism HTN
Glucose Intolerance/DM Dyslipidemia Acne Anxiety/Depression Peripheral Edema Metabolic Syndrome
specific signs of cushings syndrome
focus on these
Plethoric/moon facies Wide (>1 cm), violaceous striae (abdominal, axillary) Spontaneous Ecchymoses Proximal Muscle Weakness Early/Atypical Osteoporosis (atraumatic rib fx)
screening tests for cushings
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.)
Cushings Disease work up
ACTH LEVEL
1. Plasma ACTH levels are usually high-normal to mildly elevated in Cushing’s disease
IMAGING
2. Pituitary MRI (~80% microadenomas, 50% identified on MRI)
INFERIOR PETROSAL SINUS SAMPLING
3. For a negative/equivocal MRI
Central Adrenal Insufficiency (AI)
-etiology of secondary AI
Etiologies of Primary AI-separate lecture
Etiologies of Secondary/Tertiary AI
- Suppression of the HPA axis
- S/p tumor resection for Cushing’s Syndrome (pituitary, ectopic or adrenal)
- Supraphysiologic exogenous glucocorticoid use (most common) > 5-7.5 mg prednisone (or equivalent glucocorticoid dose) for >1 month
- Drugs: Opioids and megace - Hypothalamus/Pituitary Diseases and/or their treatments.
- Other-Isolated ACTH deficiency (very rare)
Central Adrenal Insufficiency Clinical Presentation of secondary/tertiary adrenal insufficiency (AI)
Fatigue
Anorexia, nausea/vomiting and weight loss
Generalized malaise/aches
Scant Axillary/Pubic hair (DHEA-S dependent in females)
Hyponatremia and Hypoglycemia
Central Adrenal Insufficiency work up
Basal Testing: Random a.m. cortisol level, 18 ug/dl (excludes AI diagnosis), additional provocative testing required for equivocal results.
Stimulation Tests
Insulin-induced hypoglycemia (gold standard)–assesses entire hypothalamic-pituitary-adrenal axis.
Cosyntropin (synthetic ACTH 1-24) stimulation test-valid for assessing HPA axis only if prolonged (several weeks-months) loss of pituitary signaling and resulting adrenal atrophy.
Hypogonadism Differential Dz
High FSH/LH
Low FSH/LH
High FSH/LH
- Congenital Anorchia
- Klinefelter’s Syndrome
- Testicular Injury
- Autoimmune Testicular Dz
- Glycoprotein Tumor (rarely)
Low FSH/LH
Hypogonadotropic Hypogonadism Hypothalamic/Pituitarydiseases -Macroadenomas, prolactinomas, XRT
-Isolated GnRH Deficiency (Kallman’s=anosmia vs. Idiopathic)
-Hemochromatosis
“Functional” Deficiency-
Critical Illness, OSA, starvation, Meds-opiates, glucocorticoids
Hypogonadism clinical features
- Men
- Women
Male
Reduced libido
Erectile dysfunction
Oligospermia or azoospermia
Infertility
Decreased muscle mass, testicular atrophy and decreased BMD
Hot flashes with acute and severe onset of hypogonadism
FEMALES Anovulatory cycles oligo/amenorrhea, infertility Vagina dryness, dyspareunia Hot Flashes Decreased libido Breast atrophy Reduced bone mineral density (BMD)
LH/FSH (Gonadotropin) Excess
Clinical Presentation of Gonadotrope Adenomas The majority of FSH/LH tumors are clinically silent (?inefficient intact LH/FSH hormone synthesis or secretion). Rare presentation (from functionally-intact FSH/LH molecules) include: ovarian hyper-stimulation syndrome (females) or macro-orchidism (males). Middle-aged patients (males >females) with macroadenomas and related mass effects (e.g., headaches, vision loss, cranial nerve palsies, and/or pituitary hormone deficiencies).
Thyrotropin (TSH) Elevation
Secondary
Thyrotropin secreting pituitary tumor-very rare (
Central hyperthyroidism
Clinical Presentation
Thyrotropinoma (TSHoma)-similar clinical presentation to primary hyperthyroidism (e.g., goitre, tremor, weight loss, heat intolerance, hair loss, diarrhea, irregular menses) but also with associated mass effects (e.g., headaches, vision loss, loss of pituitary gland function) from macroadenoma.
Diagnosis
Elevated Free T4 and a non-suppressed TSH
Pituitary MRI (>80% macroadenomas)
Central TSH deficiency
- etiology
- clinical presentation
Etiologies
- Pituitary/Hypothalamic Diseases and/or their treatments
- Critical Illness/Starvation-Euthyroid Sick Syndrome
- Congenital defects (TSH-beta mutations, PROP1, POUF1 mutations). Pediatric onset
- Drug induced-supraphysiologic steroids, dopamine, rexinoids.
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
Hypopit overview
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
Apoplexy
Definition: Clinical syndrome of
headache, vision changes, ophthalmoplegia and altered mental status
caused by the sudden hemorrhage or infarction of the pituitary gland.
Occurs in ~10-15% of pituitary adenomas; sub-clinical disease is more common
Diagnosis: Pituitary MRI or CT
Treatment
Emergent surgery is indicated for evidence of severe vision loss, rapid clinical deterioration, or mental status changes.
Stress dose steroids for adrenal insufficiency.
Chronology of hypo pit loss
GH, LH/FSH->TSH, ACTH->PRL
Hypo pit clinical presentation
-similar presentation to target gland hormone deficiency, with some exceptions:
-Primary adrenal insufficiency also presents with hyperkalemia from mineralcorticoid deficiency and hyperpigmentation from ACTH excess.
Diagnosis: Basal and Dynamic Testing
Hypo Pit management
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).
Prolactin – SQ formulation, research purposes only.
causes 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
Miscellaneous-Nausea, Stress and Pain
SIADH clinical presentation
Depends on the severity of hyponatremia and the rapidity of development (acute,
SIADH DX
Criteria
- Hyponatremia (Na+ 135 mmol/L) (hypotonic plasma (100mOSm/kg)with normal renal fcn
- Euvolemic Status (no orthostatics hypotension)
- Exclusion of other potential causes of euvolemic hypo-osmolality
- —Hypothyroidism
- —Hypocortisolism
SIADH TX
Identify and Reverse Underlying Disorder (when possible)
Tx depends on the severity of hyponatremia
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+ = 120mmol/L) -hypertonic saline
Diabetes Insipidus (DI)
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 Primary Polydipsia
Clinical Significance: Can lead to severe dehydration if thirst mechanisms are impaired, or if the patient has limited access to water.
DI causes
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
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
Triphasic response to stalk trauma from pituitary surgery
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 (
Outpatient DI DX
Confirm polyuria with 24 hr urine volume collection (normalized to creatinine)
Exclude hyperglycemia (osmotic diuresis), renal insufficiency and electrolyte disturbances (K+/Ca 2+)
Assess Urine and Plasma Osmolalities
Consider Water Deprivation Test
Pituitary Imaging (for suspected neurogenic DI)
DI treatment
DDAVP
