Kinder Endo CIS Flashcards
we have a concern of prolactinemia in a patient. What labs should we order?
pituitary hormones
PRL especially but also the TRH (can increase prolactin)
liver enzymes
what should we check in a woman who has not had menses in 3 months?
pregnancy
Differential Diagnosis of Sella Turcica Mass
Pituitary Adenoma Pituitary Hyperplasia Craniopharyngioma Meningioma Germ Cell Tumor Chordoma Primary Lymphoma Cyst Abscess Arteriovenous Fistula of the Cavernous Sinus
Hyperprolactinemia etiologies
Physiologic Pituitary and hypothalamic disorders Systemic disorders Pharmacologic (esp. antipsychotics, anticonvulsants) Toxins Inheritable
physiologic causes of hyperpolactinemia
Pregnancy Lactation Breast stimulation/breastfeeding Sexual activity Exercise Sleep Stress Eating
Pituitary and hypothalamic disorders that cause hyperprolactinemia
Tumors of the Pituitary:
Prolactinoma
Micro or Macroadenoma
Nonprolactin macroadenoma due to stalk compression
Adenoma with multihoromone secretion
E.g. 25% of tumors that secrete growth hormone also secrete prolactin
Other tumors (that block the path of dopamine to the pituitary): Craniopharyngioma, meningioma, germinoma, and metastatic
Infiltrative diseases
Sarcoidosis, tuberculosis, and Langerhans cell histiocytosis
Radiation Trauma Surgery Rathkes cyst Empty sella syndrome (pituitary is squished, stretching the stalk) Lymphocyctic hypophysitis Pseudotumor cerebri
Systemic Disorders leading to hyperprolactinemia
Chest wall Trauma, surgery, nipple piercing, and herpes zoster Renal failure Cirrhosis Seizures PCOS Adrenal insufficiency Hypothyroidisim Pseudocyesis- false pregnancy
drugs leading to hyperprolactinemia
Antipsychotics (dopamine antagonists) Antidepressants Anticonvulsants Opiates H2 Blockers Estrogens Protease inhibitors
heavy metals that can cause hyperprolactinemia
E.g barium, lead
genetic disorders leading to hyperprolactinemia
Multiple endocrine neoplasia type I – Autosomal Dominant
Parathyroid tumors, gastropancreatic tumors, and anterior pituitary tumors
Carney complex – Autosomal Dominant
Myxomas, increased endocrine activity, schwannomas, and spotty skin pigmentation
McCune-Albright syndrome – Random mutation of GNAS gene
Fibrous dysplasia of bone, endocrine abnormalities, and café au lait spots
where do the dopamine-secreting neurons reside?
hypothalamus
hyperprolactinemia secondary causes
Inhibition of dopamine release by hypothalamus
- Medications
- Estrogen
- Breast Stimulation
Interruption of dopamine delivery from hypothalamus to pituitary
- “Stalk effect”, e.g. secondary to trauma
Increased TRH release
- Hypothyroidism
Prolactin secreting tumors
Decreased renal or hepatic clearance
physiologic and pathologic effects of prolactin
Physiologic Effects of Prolactin
Induces and maintains lactation
Inhibits release of FSH and LH
Reduces gonadal steroidgenesis
Pathologic Effects of Prolactin
Galactorrhea, gynecomastia
Amenorrhea
hypogonadism
treatment of prolactinonma
Dopamine Agonists are first line treatment
- Cabergoline preferred over bromocriptine (longer half-life)
- Should be discontinued with pregnancy
Estrogen or testosterone therapy for long-term hypogonadism secondary to drug induced hyperprolactinemia
Surgery when unresponsive to medications
Radiation therapy for prolactinomas that are aggressive, malignant, or unresponsive to surgery
treatment monitoring for prolactinoma
Serum prolactin levels in one month
Repeat prolactin level every 4-6 months
If levels not normalized after 6 months, consider surgery
MRI at 3 months for macroadenoma or 1 year for microadenoma, repeat sooner for increased galactorrhea, visual disturbances, or headaches
Visual field testing
how long do we treat for prolactinoma?
Indication for stopping dopamine agonist:
Consider tapering after 2 or more years of treatment
- Normal prolactin level
- No tumor remnant on MRI
Stop after menopause in women with microadenoma
Discontinue with pregnancy
Dopamine agonist tapering:
Reduce by 50% over 3 months and check prolactin levels
Discontinue after 1 year at reduced dosage if prolactin normal
Check prolactin level every 3 months for one year, then yearly
MRI if prolactin level elevated
hyperpolactinemia presentation in men, elderly, post-menopausal, children
Men
- Erectile dysfunction, reduced libido, and gynecomastia
Elderly Men
- Headache, vision loss, and osteoporotic fractures
Postmenopausal Women
- Headache, vision loss, and osteoporotic fractures
- Decreased libido, vaginal dryness, and dyspareunia
Children
- Menstrual irregularities or amenorrhea
- Galactorrhea
- Headache
What is the mechanism of bitemporal hemianopsia?
pressure in the optic chiasm
acromegaly- lab testing
Serum insulin-like growth factor-1(IGF-1) level
Growth hormone after Oral Glucose Tolerance Testing
75 g of oral glucose given to patient
- Check growth hormone level every 30 minutes for 2 hours
- Growth hormone under 1 mcg/L after oral glucose tolerance test is considered normal
Prolactin level
- 25% of acromegaly patients have hyperprolactinemia
Calcium level
- Assess for hyperparathyroidism and MEN I
Blood Glucose
Anterior and Posterior Pituitary Function
- TSH and FT4
- Cortisol
- Usom/Posm (normal 1-3; <1 Diabetes insipidus)
Amenorrhea and galactorrhea in Acromegaly
Growth hormone stimulation of the prolactin receptor
Growth hormone adenoma may cosecrete prolactin
Macroadenoma may push on the pituitary stalk and block dopamine secretion
Interference with gonadotropin secretion by the pituitary
typical findings in acromegaly
Increasing hat and glove size, macroglossia, hands and feet are enlarged,
Fingers with tufting on x-rays, and skin tags
Change in bite, snoring at night, dental malocclusion, frontal bossing and a deep sonorous voice…
Acanthosis nigricans and skin tags
Etiologies of Acromegaly
Pituitary adenoma >90% Familial Syndromes: - McCune-Albright Syndrome - Carney’s Syndrome - Familial acromegaly Pituitary Carcinoma – rare Pancreatic islet cell tumors Lymphoma Somatotroph hyperplasia caused by excess GHRH by - Hypothalamic tumors - Peripheral neuroendocrine tumors ----Pheochromocytoma ----Medullary thyroid carcinoma ----Adrenal adenoma ----Small cell lung cancer ----Bronchial carcinoid Exogenous use of human growth hormone
Complications of a growth hormone secreting adenoma
Direct tumor effect
- Headaches
- Visual disturbances
Additional Hormone production
- Prolactin
Interference with other hormones
- Decreased ACTH, TSH, and other hormones
Growth hormone adenoma Associated Conditions
Multiple endocrine neoplasia type I
- Pituitary adenoma, hyperparathyroidism, and pancreatic islet cell adenomas
Hyperprolactinemia
- 25% of growth hormone secreting adenomas cosecrete prolactin
McCune-Albright syndrome
- Triad of café au lait skin changes, precocious puberty, and fibrous dysplasia
Malignancy
- Thyroid cancer, bladder, and kidney
Carney Syndrome
- Cutaneous pigmentation, fibromyxoid tumors of the skin, myxomas of the heart, and endocrine overactivity
acromegaly Treatment
Surgery is the treatment of choice using a transsphenoidal approach.
Medical Treatment - Octreotide – somatostatin analog - Dopamine agonists – cabergoline - Growth hormone receptor antagonist – pegvisomant Radiation Therapy
follow up monitoring of growth hormone adenoma
Annual MRI
Annual testing of IGF-1 and Growth Hormone
Consider OGTT and GH
Signs and symptoms of Acromegaly
Tumor Mass Effect - Visual Loss - Cranial Nerve Palsies - Hypopituitarism Coarsening of facial Features -- Frontal bossing/widening of nose Prognathism, tooth separation, dental occlusion Macroglossia Deepening of the voice Acral enlargement and thickening of the skin Depression Headaches Arthralgias, joint hypermobility, arthropathy, carpal tunnel syndrome Goiter/Thyroid nodules Sleep Apnea, snoring Hyperhidrosis, skin oiliness, skin tags Hypertension, LVH, Valvular disease, Heart Failure Hypogonadism(low sex hormone binding globulin) and menstrual irregularities Hyperprolactinemia/galactorrhea Insulin resistance and diabetes Hypertriglyceridemia Hypercalciuria/hyperphosphatemia Osteoporosis/vertebral fractures Increased colon polyps Fatigue
dx for polyuria
Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Psychogenic Polydipsia Osmotic Diuresis - Diabetes Mellitus Hypercalcemia or Hypokalemia Decreased aldosterone production Increased Cortisol Post-obstructive Diuresis Post renal failure Drugs: - Lithium - Demeclocycline - Cis-platinum - Diuretics Caffeine Ethanol
Osmolality Calculation
2[Na] + [Glucose]/18 + [BUN]/2.8
testing in polyuria
Confirm hypotonic polyuria with 24 hour urine for volume and osmolality
Check serum electrolytes, BUN, Creatinine and glucose
- Calculate serum osmolality
If serum osmolality (> 295 mOsm/kg) and high plasma sodium levels (>143 mEq/L)
- Primary polydipsia unlikely
- Vasopressin challenge test to confirm central diabetes insipidus and distinguish it from nephrogenic diabetes insipidus
If plasma osmolality and serum sodium normal, induce hyperosmolar states with a water deprivation test or hypertonic saline infusion, then proceed with a vasopressin challenge test
24-hour urine for volume and osmolality
Urine volume typically greater than 3 liters per day in diabetes insipidus
Urine osmolality < 300 mOsm/kg
Water Deprivation Test
Not needed if elevated plasma osmolality (>295 mOsm/kg), high sodium level (>143 mEq/L), and low urine osmolality
– Go straight to the vasopressin challenge test
Check plasma arginine vasopressin level at baseline
Monitor weight, blood pressure, heart rate, serum sodium, plasma osmolality, urine osmolality, and urine volume hourly
Stop test for any of the following
Body weight decreases by 3-5%
Orthostatic blood pressure changes
Urine osmolality plateaus (less than 10% change over 3 consecutive measurements)
Urine osmolality normalizes (> 750 mOsm/kg)
Plasma osmolality > 295-300 mOsm/kg
Serum sodium > 143-145 mEq/L
Check plasma arginine vasopressin level at the end of the test
Stop water deprivation test for any of the following
Body weight decreases by 3-5%
Orthostatic blood pressure changes
Urine osmolality plateaus (less than 10% change over 3 consecutive measurements)
Urine osmolality normalizes (> 750 mOsm/kg)
Plasma osmolality > 295-300 mOsm/kg
Serum sodium > 143-145 mEq/L
Check plasma arginine vasopressin level at the end of the test
interpreting water deprivation test
Little or no increase in urine osmolality (under 300 mOsm/kg) consistent with complete diabetes insipidus
Small increase ( 400-500 mOsm/kg) consistent with partial diabetes insipidus or primary polydipsia
Normal individuals
- Serum osmolality increased
- Urine osmolality maximized to > 800 mOsm/kg
- No increase in urine osmolality with administration of arginine vasopressin
Vasopressin/desmopressin challenge test
Perform in hyperosmolar states after water deprivation test
Administer vasopressin or DDAVP
Check urine osmolality every 30 minutes for 2-4 hours
If urine osmolality increases > 50%, likely central diabetes insipidus
If no change in urine osmolality, likely nephrogenic diabetes insipidus
If urine osmolality increases by under 50% may be partial central or nephrogenic diabetes insipidus
Central Diabetes Insipidus etiologies
Idiopathic 20-50%
Lymphocytic hypophysitis:
- Primary – unknown etiology (20% associated with thyroiditis, hypoparathyroidism, vitiligo, pernicious anemia, myasthenia gravis, or systemic lupus erythematosis)
- Secondary (Sarcoidosis, Langerhans cell histiocytosis, Viral, fungal, bacterial, Tb)
Trauma/Surgery
CNS neoplasms/Leukemia
Hypoxic injury
Meningitis/Encephalitis
Vascular – Internal carotid aneurysm
Congenital: Wolfram Syndrome (DIDMOAD)
- Rare autosomal recessive
- DI
- DM
- Optic Atrophy
- Deafness
Stalk thickening may be seen with?
Lymphocytic hypophysitis/Infiltrative Disorders/Autoimmune
Treatment of Central Diabetes Insipidus
Desmopressin(DDAVP)
- Synthetic analog of arginine vasopressin(AVP)
- Titrated to control polyuria and polydipsia
- Patients should drink no more than is necessary to satisfy thirst to avoid hyponatremia
Other treatments
- Carbamazepine
- Chlorpropamide
- Hydrochlorothiazide
Etiology of Nephrogenic Diabetes Insipidus
Lithium Therapy
- 55% of patients on long term lithium therapy
Metabolic
- Hypercalcemia, hypercalciuria, and hypokalemia
Release of Urinary Obstruction
Protein Malnutrition
Aging
Chronic Pyelonephritis
Other Drugs
- Demeclocycline, rifampin, cisplatin, amphotericin B
Infiltrative Conditions
- Amyloidosis, sarcoidosis, or sarcoma
Vascular Disease
- Sickle cell disease, ischemia
Congenital
- Arginine vasopressin receptor 2 mutations (X-linked)
- Aquaporin-2 water channel gene mutations
- Urea transporter-B gene mutations
Signs and Symptoms of Hypopituitarism
loss of growth hormone, gonadotropin, TSH, ACTH
Growth Hormone Loss–>
Decreased sense of well being Decreased muscle and bone mass Increased central fat Decreased cardiac output Increased cholesterol
Gonadotropin Loss–>
Fine wrinkling of the skin Decreased Libido Hair Loss Gynecomastia Atrophic Testes Vaginal Dryness Alopecia
TSH Loss–>
Fatigue Constipation Dry skin Puffiness Alopecia Cold Intolerance Weight gain Increased Cholesterol
ACTH Loss–>
Weakness Fatigue Low grade fever Orthostasis Loss of genital hair Pallor Hypoglycemia Abdominal pain Nausea/vomiting Weight loss Low Na, normal K
Etiology of Anterior Pituitary Failure
Pituitary Tumors Non Pituitary Tumors (Craniopharyngioma, Meiningioma, Glioma, Chordoma, Epednymoma, Germinoma, Metastasis) Traumatic Brain Injury Neurosurgery Subarachnoid hemorrhage Stroke Cranial Radiation Postpartum hemorrhage- Sheehan syndrome Empty Sella Syndrome Inflammatory conditions (Sarcoidosis, Hypophysitis, Tuberculosis, Granulomatosis with polyangiitis) Infections (Abscess, Meningitis, Encephalitis) Pituitary apoplexy Carotid aneurysm Hemochromatosis Histiocytosis X Granulomatous diseases Idiopathic Congenital (Pituitary hypoplasia, Holoprosencephaly, Asphyxia/abnormal delivery, Genetic- PROP1 mutations)
in what order do we lose anterior pituitary failure
GH
Gonadotropins
thyroid
ACTH
replace them in reverse order
Testing for Anterior Pituitary Hormone Deficiencies
Basal Secretion Tests, Stimulation Tests
Basal Secretion Tests
IGF-I FSH and LH Early AM serum testosterone in males and estradiol in females TSH and Free T4 Morning serum or salivary cortisol Morning plasma ACTH Basal serum prolactin levels
Stimulation Tests
Insulin Tolerance Test
Glucagon stimulation test
ACTH stimulation test (cosyntropin test)
Serum prolactin level after injection with TRH
Growth Hormone Deficiency stimulation tests
Low IGF-I (under 85mcg/L)
Stimulation Tests may be needed: Insulin Tolerance Test Glucagon Stimulation Test Exercise GH < 5 ng/mL confirms deficiency
Gonadotropin Hormone Deficiency testing
Exclude hyperprolactinemia
Males:
Exclude low sex hormone-binding globulin
Early morning testosterone level < 280 ng/dL
Low or normal LH and FSH
Females:
Serum estradiol under 27 pg/mL
Low or normal LH and FSH
Thyroid-stimulating hormone deficiency testing
Serum TSH
Free T4
Low T4 without an elevation of TSH consistent insufficiency of TSH
ACTH hormone deficiency testing
AM cortisol level (6-9 AM)
- 18.1 mcg/dL intact hypothalamic-pituitary-adrenal axis
- 2.9-18.1 mcg/dL require further testing
- under 3 mcg/dL indicate adrenal insufficiency
Plasma ACTH (6-9 AM)
- > 100 pg/mL indicates primary adrenal insufficiency
- under 50 pg/mL indicates secondary adrenal insufficiency
ACTH stimulation test (cosyntropin test)
- ACTH 250 mcg IV or IM
- Measure cortisol 30-60 minutes later
- Normal – peak cortisol 18.1-21.7 mcg/dL
- Adrenal insufficiency – peak cortisol < 18 mcg/dL
prolactin and hypopituitarism
Prolactin level may be high or low in hypopituitarism
