Kinder CIS Flashcards
Secondary Hypertension causes
Renal parenchymal disease Renal artery stenosis Obstructive sleep apnea Endocrine: - Hyperaldosteronism - Thyroid disease - Cushing disease Pheochromocytoma Coarctation of the aorta CNS (Brain Tumor) Medications (NSAID) Polycythemia Pre-eclampsia Hypercalcemia (renal dysfunction and vasoconstriction)
what is essential hypertension?
idiopathic
Primary Aldosteronism – Who to screen
Blood pressure ≥ 150/100 mm Hg on 3 separate occasions
Drug Resistant Hypertension
BP > 140/90 mm Hg that is resistant to 3 medications including a diuretic
Controlled blood pressure on 4 medications
Hypertension and hypokalemia
Hypertension with an adrenal incidentaloma
Hypertension and sleep apnea
Hypertension with a family history of early onset hypertension or stroke age under 40
Hypertension and first-degree relative with primary aldosteronism
testing aldosteronism- Test Preparation
Correct hypovolemia and hypokalemia
Stop spironolactone, eplerenone, amiloride, potassium wasting diuretics, licorice, and chewing tobacco at least one month before testing
Patient should be ambulatory and sitting upright with a morning sample
Substitute antihypertensives:
Verapamil, hydralazine, and doxazosin
Etiologies of Primary Hyperaldosteronism
Unilateral aldosterone-producing adenoma ≅ 50%
Bilateral Adrenal Hyperplasia ≅ 50%
Rarer:
Inherited glucocorticoid-remedial aldosteronism
- ACTH instead of angiotensin II regulated
- Suppressed by low dose glucocorticoids
Unilateral adrenal hyperplasia
Bilateral aldosterone producing adenomas
Adrenocortical carcinoma
tests to confirm primary hyperaldosteronism
Oral Salt Loading Test – most common test
Saline Suppression Test
Fludrocortisone Suppression Test
Oral Salt Loading Test
6 gm salt per day for 3 days
Maintain normokalemia
24-hour urinary aldosterone > 12 mcg/day suggestive of primary aldosteronism
Saline Suppression Test
2 liters normal saline infusion over 4 hours
Plasma aldosterone ≥ 10 ng/dL confirms primary aldosteronism
Fludrocortisone Suppression Test
Fludrocortisone 0.1 mg po q 6 hours for 4 days
NaCl 1800 mg po tid, High Salt Diet, Supplemental Potassium
Plasma aldosterone > 6 ng/dL day 4 consistent with primary aldosteronism
Adrenal Venous Sampling
Best test to determine if small adenoma on CT is secreting aldosterone
Differentiate between bilateral or unilateral hyperplasia
treating adrenal hyperplasia
Treat hypertension and hypokalemia with spironolactone and oral potassium supplementation
Unilateral laparoscopic adrenalectomy for unilateral adrenal hyperplasia or unilateral aldosterone producing adenoma
11-β-hydroxysteroid dehydrogenase 2
Enzyme expressed in aldosterone-selective epithelial tissues such as kidney, colon, salivary, and sweat glands.
Oxidizes cortisol to the inactive metabolite cortisone preventing illicit activation of the mineralcorticoid receptor.
Glycyrrhizinic acid in black licorice inactivates 11-β-HSD 2 causing pseuodohyperaldosteronism
Syndrome of apparerent mineralocorticoid excess is caused by a genetically inherited deficiency of 11-β-HSD 2
Liddle Syndrome
Autosomal Dominant
Dysregulation of epithelial sodium channel (ENaC) due to a genetic mutation that causes the channels to no longer be degraded appropriately
High number of channels present in the collecting ducts lead to pseudohyperaldosteronism (↓PRA, ↓PAC)
Treatment is with potassium sparing diuretics
- Amiloride
- Triamterene
17 alpha hydroxylase deficiency
mineralocorticoids up
cortisol and sex hormones down
hypertension
hypokalemia
decreased DHT
male: ambiguous genitalia, pseudo-hermaphroditism
female: lack of 2ndary sexual characteristics
21-hydroxylase deficiency
decreased mineralocorticoids, decreased cortisol
increased sex hormones
hypotension
hyperkalemia
increased renin activity
increased 17-hydroxyprogesterone
presents in infancy
- salt wasting
- precocious puberty
- female: virilization
11 beta hydroxylase enzyme deficiency
decreased aldosterone
increased 11-deoxycorticosterone
decreased cortisol
increased sex hormones
hypertension with low renin
female virilization
Hirsutism
Due to decreased sex hormone binding globulin leading to increased free testosterone
Decreased estrogen (e.g. prolactinoma) Insulin Growth Hormone (acromegaly) Obesity (especially PCOS) Hypothyroidism Glucocorticoids (Cushings) Androgens Nephrotic Syndrome
causes of hirsutism
PCOS (70-80% of cases)
- Irregular menses, central obesity, infertility, acanthosis nigricans, and insulin resistance
Idiopathic hyperandrogenemia (6-15% of cases) - Clinical and biochemical signs of hyperandrogenemia with regular ovulatory cycles
Idiopathic hirsutism (50% of mild cases) - Normal androgens, normal ovulation, normal appearing ovaries
Congenital Adrenal Hyperplasia (< 5% of cases)
- Menstrual dysfunction and anovulation
Rare etiologies of hirsutism
Acromegaly Cushing syndrome Hyperprolactinemia Hyperthecosis Thyroid dysfunction Glucocorticoid resistance
Drugs - Anabolic Steroids - Androgenic steroids - Valproic acid Androgen secreting adrenal or ovarian tumor
Labs for patients with hirsutism
Fasting Glucose/Insulin TSH Prolactin IGF-1 24 hour urine Cortisol
Testosterone
DHEAS
17OHP
of those last three tests:
Idiopathic or hereditary - all normal
PCOS (LH/FSH > 2) - testosterone mildly increased
CAH - all increased (17 OHP > 500* ng/dL = CAH)
Virilization:
Increased muscularity, temporal alopecia, deepening voice, acne, clitoromegaly - Adrenal, Ovaries, CAH
Labs usually show increase of:
testosterone (ovarian neoplasm)
DHEAS (adrenal neoplasm)
androstenedione (adrenal or ovarian)
Labs for patients with virilization
- Ovarian tumor
total testosterone greatly increased with normal
DHEAS and 17 OHP. (Total Testosterone > 200 ng/dL points to ovary or adrenal) - Adrenal tumor
greatly increased DHEAS (> 700ng/dL) - CAH
Total Testosterone, DHEAS, and 17 OHP = all increased.
(17 OHP > 500 ng/dL = diagnostic)
Labs for patients with hirsutism or virilization
** Total testosterone > 200 ng/dL = ovarian neoplasm
Serum androstenedione > 1000 ng/dL = adrenal or ovarian neoplasm
** DHEAS > 700mcg/dL = adrenal neoplasm or CAH
17-hydroxyprogesterone = CAH **(> 500 ng/dL is diagnostic); CAH usually has base line > 300ng/dL with ACTH stimulated to > 1000 ng/dL)
ACTH and 24 hour urine cortisol
LH:FSH > 2 (PCOS)
TSH, prolactin,
Treatment of Hirsutism
Combination Oral Contraceptives
Antiandrogens
- Spironolactone
- Finasteride (5-alpha reductase inhibitor)
- Metformin (reduces hepatic gluconeogenesis)
—- Lowers peripheral insulin sensitivity
—- Lowers insulin levels
—- Not great for hirsutism
GnRH agonists (decrease gonadotropins by constant stimulation)
Pheochromocytoma symptoms
Classic Triad of Symptoms:
Paroxysmal headache, palpitations, and sweating
Other paroxysmal symptoms:
Anxiety, pallor/flushing, syncope, tremor, blurred vision, heat intolerance, nausea, vomiting, abdominal pain, diarrhea, constipation, polyuria, polydipsia, weight loss, fatigue, chest pain, low grade fever
labs to confirm pheochromocytoma
24 hour Urinary Fractionated Metanephrines or Plasma Free Metanephrines
- Metaneprhine (epinephrine metabolite)
- Normetanephrine (norepinephrine metabolite)
Other testing
- 24 hour urine catecholamines
- – Norepinephrine, epinephrine, and dopamine
- 24 hour urine vanilylmandelic acid (norepineprhine metabolite) , homovanillic acid (dopamine metabolite)
pheochromocytoma treatment goals
get blood pressure and heart rate down
less than 1 PVC every 5 minutes on EKG
No S-T segment changes or T-wave inversions on EKG
meds for pheochromocytoma
Alpha-adrenergic blocker - 1st
Phenoxybenzamine
Beta-adrenergic blocker – 2nd
Atenolol
Increase intake of salt and fluid for volume expansion if needed
Precipitators of adrenergic crisis
Postural changes or increase in intra-abdominal pressure Exertion, Trauma Foods/Beverages --- Banana, cheese, caffeine Emotional Stress Urination(bladder pheochromocytoma) Drugs --- Corticosteroids, metoclopramide, phenothiazines, tricyclic antidepressants, sympathomimetics, morphine, nasal decongestants, glucagon, chemotherapeutic agents Induction of anesthesia Manipulation of the tumor
where pheochromocytomas arise
80-85% of pheochromocytomas arise in the adrenal
10-20% :
symphathetic ganglia in pelvis, mediastinum, or neck
Along cranial nerves
Vagus (parasympathetic)
Most common site in the abdomen is at the origin of the inferior mesenteric artery
Pheochromocytoma Rules of 10
10% Extra-adrenal 10% Bilateral 10% Malignant 10% Children 10% Familial 10% not associated with hypertension 10% contain calcification
Genetic Disorders associated with Pheochromocytomas
MEN 2A
MEN 2B
Von Hippel Lindau Syndrome
Hereditary Paraganglioma-Pheochromocytoma Syndromes
Multliple Endocrine Neoplasia 2A (Autosomal Dominant)
Mutation of germline RET (neural crest cells)
Pheochromocytoma
Parathyroid Tumors
Medullary Thyroid Cancers
Multiple Endocrine Neoplasia 2B (Autosomal Dominant)
Mutation of germline RET
Medullary Thyroid Cancers
Pheochromocytoma
Mucosal Neuroma
Intestinal ganglioneuromas
Muscle, joint, and spinal problems – Marfinoid body habitus
Facial Features including swollen lips, and thick eyelids
Von Hippel-Lindau Syndrome – Autosomal Dominant
Retinal angiomatosis Cerebral hemangioblastoma Pheochromocytoma Renal cyst/Carcinoma Pancreatic cysts Endolymphatic sac tumor Bilateral papillary cystadenomas of the epididymis in men and broad limagment of the uterus in women Genetic: VHL
Hereditary Paraganglioma-Pheochromocytoma Syndromes
Autosomal Dominant
Paragangliomas in the skull base, upper mediastinum, and neck are usually parasympathetic and generally do not secrete.
Paragangliomas in the lower mediastinum, abdomen, and pelvis are typically associated with the sympathetic nervous system and hypersecrete catecholamines
Gynecomastia etiologies
Physiologic - 25% - Neonatal, pubertal, or aging - 90 % newborns, 50% of boys during puberty, 65% of hospitalized men age 50-80 Idiopathic – 25% Medication- 10-25% Cirrhosis 8 % Hypogonadism Tumors Hyperthyroidism Chronic Renal Insufficiency Obesity
Drugs: Cimetidine Finasteride Cannabinoids Omeprazole Ranitidine Spironolactone Diazepam Phenytoin Phenothiazines Opioids
Testing for gynecomastia
Pubertal Gynecomastia
Does not need further testing in most cases
Testing when etiology unclear: Liver and kidney function Thyroid function Testosterone, LH, FSH, and Prolactin Serum estradiol Beta-HCG, AFP - rule out germ cell tumors DHEA-Sulfate – adrenal androgens
Testicular Ultrasound
- Testicular mass
- Gynecomastia > 5 cm
- Elevated hCG
- Elevated estradiol
- Unclear etiology for gynecomastia
Breast Cancer suspicion
- Breast ultrasound and mammogram
- Biopsy
Abdominal CT if adrenal tumor suspected
treatment of gynecomastia
Pubertal boys reassurance and watchful waiting
Asymptomatic men with long standing gynecomastia no treatment necessary
Stop offending medications
Medications
- Antiestrogens – tamoxifen or raloxifene
- Androgens – danazol
Surgery
