Kinder Endo CIS

Question 1

we have a concern of prolactinemia in a patient. What labs should we order?

Answer 1

pituitary hormones
PRL especially but also the TRH (can increase prolactin)

liver enzymes

Question 2

what should we check in a woman who has not had menses in 3 months?

Answer 2

pregnancy

Question 3

Differential Diagnosis of Sella Turcica Mass

Answer 3

Pituitary Adenoma
Pituitary Hyperplasia
Craniopharyngioma
Meningioma
Germ Cell Tumor
Chordoma
Primary Lymphoma
Cyst
Abscess
Arteriovenous Fistula of the Cavernous Sinus

Question 4

Hyperprolactinemia etiologies

Answer 4

Physiologic
Pituitary and hypothalamic disorders
Systemic disorders
Pharmacologic (esp. antipsychotics, anticonvulsants)
Toxins
Inheritable

Question 5

physiologic causes of hyperpolactinemia

Answer 5

Pregnancy
Lactation
Breast stimulation/breastfeeding
Sexual activity
Exercise
Sleep
Stress
Eating

Question 6

Pituitary and hypothalamic disorders that cause hyperprolactinemia

Answer 6

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

Question 7

Systemic Disorders leading to hyperprolactinemia

Answer 7

Chest wall
Trauma, surgery, nipple piercing, and herpes zoster
Renal failure
Cirrhosis
Seizures
PCOS
Adrenal insufficiency
Hypothyroidisim
Pseudocyesis- false pregnancy

Question 8

drugs leading to hyperprolactinemia

Answer 8

Antipsychotics (dopamine antagonists)
Antidepressants
Anticonvulsants
Opiates
H2 Blockers
Estrogens
Protease inhibitors

Question 9

heavy metals that can cause hyperprolactinemia

Answer 9

E.g barium, lead

Question 10

genetic disorders leading to hyperprolactinemia

Answer 10

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

Question 11

where do the dopamine-secreting neurons reside?

Answer 11

hypothalamus

Question 12

hyperprolactinemia secondary causes

Answer 12

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

Question 13

physiologic and pathologic effects of prolactin

Answer 13

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

Question 14

treatment of prolactinonma

Answer 14

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

Question 15

treatment monitoring for prolactinoma

Answer 15

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

Question 16

how long do we treat for prolactinoma?

Answer 16

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

Question 17

hyperpolactinemia presentation in men, elderly, post-menopausal, children

Answer 17

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

Question 18

What is the mechanism of bitemporal hemianopsia?

Answer 18

pressure in the optic chiasm

Question 19

acromegaly- lab testing

Answer 19

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)

Question 20

Amenorrhea and galactorrhea in Acromegaly

Answer 20

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

Question 21

typical findings in acromegaly

Answer 21

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

Question 22

Etiologies of Acromegaly

Answer 22

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

Question 23

Complications of a growth hormone secreting adenoma

Answer 23

Direct tumor effect

• Headaches
• Visual disturbances

Additional Hormone production
- Prolactin

Interference with other hormones
- Decreased ACTH, TSH, and other hormones

Question 24

Growth hormone adenoma Associated Conditions

Answer 24

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

Question 25

acromegaly Treatment

Answer 25

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 ```

Question 26

follow up monitoring of growth hormone adenoma

Answer 26

Annual MRI Annual testing of IGF-1 and Growth Hormone Consider OGTT and GH

Question 27

Signs and symptoms of Acromegaly

Answer 27

``` 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 ```

Question 28

dx for polyuria

Answer 28

``` 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 ```

Question 29

Osmolality Calculation

Answer 29

2[Na] + [Glucose]/18 + [BUN]/2.8

Question 30

testing in polyuria

Answer 30

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

Question 31

24-hour urine for volume and osmolality

Answer 31

Urine volume typically greater than 3 liters per day in diabetes insipidus Urine osmolality < 300 mOsm/kg

Question 32

Water Deprivation Test

Answer 32

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

Question 33

Stop water deprivation test for any of the following

Answer 33

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

Question 34

interpreting water deprivation test

Answer 34

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

Question 35

Vasopressin/desmopressin challenge test

Answer 35

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

Question 36

Central Diabetes Insipidus etiologies

Answer 36

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

Question 37

Stalk thickening may be seen with?

Answer 37

Lymphocytic hypophysitis/Infiltrative Disorders/Autoimmune

Question 38

Treatment of Central Diabetes Insipidus

Answer 38

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

Question 39

Etiology of Nephrogenic Diabetes Insipidus

Answer 39

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

Question 40

Signs and Symptoms of Hypopituitarism

Answer 40

loss of growth hormone, gonadotropin, TSH, ACTH

Question 41

Growth Hormone Loss-->

Answer 41

``` Decreased sense of well being Decreased muscle and bone mass Increased central fat Decreased cardiac output Increased cholesterol ```

Question 42

Gonadotropin Loss-->

Answer 42

``` Fine wrinkling of the skin Decreased Libido Hair Loss Gynecomastia Atrophic Testes Vaginal Dryness Alopecia ```

Question 43

TSH Loss-->

Answer 43

``` Fatigue Constipation Dry skin Puffiness Alopecia Cold Intolerance Weight gain Increased Cholesterol ```

Question 44

ACTH Loss-->

Answer 44

``` Weakness Fatigue Low grade fever Orthostasis Loss of genital hair Pallor Hypoglycemia Abdominal pain Nausea/vomiting Weight loss Low Na, normal K ```

Question 45

Etiology of Anterior Pituitary Failure

Answer 45

``` 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) ```

Question 46

in what order do we lose anterior pituitary failure

Answer 46

GH Gonadotropins thyroid ACTH replace them in reverse order

Question 47

Testing for Anterior Pituitary Hormone Deficiencies

Answer 47

Basal Secretion Tests, Stimulation Tests

Question 48

Basal Secretion Tests

Answer 48

``` 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 ```

Question 49

Stimulation Tests

Answer 49

Insulin Tolerance Test Glucagon stimulation test ACTH stimulation test (cosyntropin test) Serum prolactin level after injection with TRH

Question 50

Growth Hormone Deficiency stimulation tests

Answer 50

Low IGF-I (under 85mcg/L) ``` Stimulation Tests may be needed: Insulin Tolerance Test Glucagon Stimulation Test Exercise GH < 5 ng/mL confirms deficiency ```

Question 51

Gonadotropin Hormone Deficiency testing

Answer 51

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

Question 52

Thyroid-stimulating hormone deficiency testing

Answer 52

Serum TSH Free T4 Low T4 without an elevation of TSH consistent insufficiency of TSH

Question 53

ACTH hormone deficiency testing

Answer 53

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

Question 54

prolactin and hypopituitarism

Answer 54

Prolactin level may be high or low in hypopituitarism