Endo E2
Pituitary Disorders
Anterior Pituitary
Regulation: Regulated by releasing and inhibiting hormones from the hypothalamus.
Secretes (Mnemonic - FLAT PEG):
FSH (Follicle-Stimulating Hormone)
LH (Luteinizing Hormone)
ACTH (Adrenocorticotropic Hormone)
TSH (Thyroid-Stimulating Hormone)
Prolactin
Endorphins
GH (Growth Hormone)
Posterior Pituitary
Function: Does not synthesize hormones. It stores and releases hormones produced in the hypothalamus.
Secretes: ADH (Vasopressin) and Oxytocin.
Key Clinical Sign of Pituitary Masses
Bitemporal Hemianopsia: Mass effect from a pituitary macroadenoma (>10mm) compressing the optic chiasm → bilateral loss of peripheral vision.
2. Anterior Pituitary Hormones
3. Pituitary Adenomas & Hyperprolactinemia
Adenomas: Benign tumors. Microadenoma (<10mm) vs. Macroadenoma (>10mm). Prolactinoma = MC secretory type.
Hyperprolactinemia Presentation:
Women: Oligomenorrhea, amenorrhea, galactorrhea, infertility.
Men: Hypogonadism, decreased libido, erectile dysfunction, gynecomastia.
Causes: Pathologic (tumors), Physiologic (pregnancy, exercise), Pharmacologic (dopamine antagonists, estrogens).
Diagnosis: Elevated fasting AM Prolactin. MRI of the brain.
Treatment:
1st Line: Dopamine Agonists (Cabergoline preferred over Bromocriptine).
2nd Line: If medication-intolerant, CSF leak, or visual field deficits → Transsphenoidal resection
4. Anterior Hypopituitarism
Panhypopituitarism → loss of all anterior pituitary hormones.
Acquired Causes: MC = Pituitary adenoma, trauma, surgery, cranial radiation, stroke.
Congenital Cause: Kallmann Syndrome (GnRH deficiency causing delayed/absent puberty paired with anosmia/lack of smell).
Symptoms (Hormone Dependent):
Gonadotropins: Infertility, delayed puberty, low libido.
ACTH: Weakness, weight loss, hypotension, low cortisol.
TSH: Hypothyroidism symptoms.
Diagnosis: Laboratory confirmation of specific hormone deficiencies (basal and provocative testing). MRI of the brain to evaluate for mass lesions or empty sella.
Treatment: Lifelong replacement of deficient hormones.
GH: Recombinant GH
ACTH: Hydrocortisone or Prednisone
TSH: Levothyroxine
Clinical Pearl: Patients with ACTH deficiency require increased "stress-dose" steroids during major physical stress or surgery to prevent adrenal crisis.
5. Growth Hormone (GH) Disorders
Growth Hormone Deficiency (GHD)
Pediatric Presentation: Growth failure after a period of normal growth. Height >2 standard deviations below median. Prominent forehead (frontal bossing), depressed midfacial development (cherubic face), increased truncal fat, delayed dentition, and delayed puberty.
Adult Presentation: Usually coincides with the discovery/treatment of a pituitary tumor. Causes reduced bone mineral density, central obesity, insulin resistance, and impaired cardiac function.
Diagnosis: Gold Standard = Insulin Tolerance Test (ITT) or specific GH stimulation (provocative) tests; Random GH levels are unreliable.
Treatment: Human growth hormone replacement.
GH Excess: Acromegaly & Gigantism
Pathology: Driven by excessive IGF-1 production, typically from a pituitary somatotroph adenoma.
Gigantism: Occurs before closure of epiphyseal growth plates in childhood. Results in abnormally high linear growth.
Acromegaly: Occurs after growth plate fusion in adulthood. Features include excessive growth of hands, feet, jaw (prognathism), macroglossia, deepened voice, and a "doughy" sweaty handshake.
Complications: Hypertension, dilated left ventricle, diabetes mellitus, obstructive sleep apnea, colon polyps.
Diagnosis: Best confirmatory test = Oral Glucose Tolerance Test (OGTT). In Acromegaly, GH fails to suppress to < 5 ng/dL.
Treatment: Somatostatin analogs (Octreotide) and Dopamine agonists; 2nd line = Transsphenoidal surgery
6. ACTH-Related Disorders
Cushing Syndrome: Caused by prolonged exposure to elevated levels of glucocorticoids. Cause can be exogenous or endogenous. MCC: Exogenous administration of corticosteroids. Endogenous causes include pituitary adenomas (Cushing's Disease).
Nelson's Syndrome: A rare condition occurring s/p bilateral adrenalectomy for Cushing's disease. The removal of the adrenals eliminates negative feedback, leading to a rapidly growing, locally invasive ACTH-secreting pituitary tumor.
Presentation: Very high levels of ACTH resulting in marked hyperpigmentation (due to MSH co-secretion), headaches, and visual field loss.
7. Posterior Pituitary: ADH Physiology
Stimulation: ADH (Vasopressin) secretion is triggered by increased plasma osmolarity (detected by osmoreceptors) and decreased blood volume/pressure.
Mechanism: Binds to receptors in the collecting ducts of the kidneys, promoting the insertion of aquaporins for water reabsorption.
Clinical Effects: Decreases plasma osmolarity, increases urine osmolarity (concentrates urine), and increases arterial BP (vasopressor effect).
8. Diabetes Insipidus (DI)
Characterized by too little ADH → Highly dilute urine, concentrated blood plasma (hypernatremia).
9. Syndrome of Inappropriate ADH (SIADH)
Characterized by too much ADH → Concentrated urine, dilute blood plasma (hyponatremia).
Pathophysiology: Inappropriate, continued secretion of ADH despite normal or increased plasma volume. Results in euvolemic hypotonic hyponatremia.
Causes: CNS disorders (trauma, infection), Neoplasia (SCLC), Pulmonary diseases, Drugs (SSRIs, Carbamazepine).
Diagnosis (Bartter-Schwartz Criteria): Hyponatremia with hypo-osmolality, continued renal sodium excretion, and absence of volume depletion.
Symptoms: Correlate with the rate of sodium drop; Ranges from confusion/weakness to seizures, coma, and respiratory arrest.
Treatment: Fluid restriction (1st line for chronic), Vasopressin-2 receptor antagonists, Loop diuretics. Emergency severe hyponatremia → Hypertonic saline.
CRITICAL WARNING: Overly rapid correction of hyponatremia (>10-12 mEq/L in 24h) can cause Central Pontine Myelinolysis → permanent neurologic impairment.
10. Sheehan Syndrome
Pathophysiology: Infarction and necrosis of the pituitary gland secondary to severe hemorrhage and hypovolemic shock during childbirth.
Initial Presentation: MC immediate symptom = failure to lactate due to prolactin deficiency. Followed by amenorrhea.
Progression: Progressive development of symptoms consistent with hypothyroidism and hypoadrenalism.
Diagnosis: Labs reveal partial or complete panhypopituitarism. MRI in long-standing cases frequently shows an "Empty Sella".
Treatment: Lifelong HRT. Crucial rule: Always replace glucocorticoids before administering levothyroxine to prevent precipitating an acute adrenal crisis.
Thyroid & Parathyroid Disorders
1. Parathyroid Hormone (PTH)
Primary Role: Calcium homeostasis. PTH raises blood calcium levels and lowers blood phosphate levels.
Mechanisms of Action:
Bone: Stimulates osteoclast activity (bone resorption), releasing calcium and phosphate into the blood.
Kidneys: Increases renal calcium reabsorption and increases phosphate excretion.
GI Tract: Stimulates the kidneys to produce active Vitamin D (Calcitriol), which then increases intestinal absorption of calcium.
2. Hyperparathyroidism
Pathophysiology: Overproduction of PTH → hypercalcemia.
Primary: Adenoma (MC, ~85%), hyperplasia, or carcinoma.
Secondary: Physiologic response to chronic hypocalcemia (MC due to CKD or severe Vitamin D deficiency).
S&S ("Stones, Bones, Abdominal Groans, Psychiatric Overtones"):
Stones: Nephrolithiasis (renal stones), nephrocalcinosis.
Bones: Bone pain, fractures, Osteitis Fibrosa Cystica (classic bone disease characterized by "brown tumors" and cystic bone spaces).
Abdominal Groans: N/V, constipation, PUD, pancreatitis.
Psychiatric Overtones: Lethargy, fatigue, depression, memory loss.
Diagnosis (Labs):
High Serum Ca2+, High PTH, Low Serum Phosphate (in primary).
Imaging: DEXA scan (for bone loss), Sestamibi scan or ultrasound (to localize adenoma before surgery).
Treatment:
Surgery: Parathyroidectomy = definitive treatment (especially for symptomatic patients or marked hypercalcemia).
Medical Management: Cinacalcet (calcimimetic), Bisphosphonates (for bone density).
Acute Hypercalcemic Crisis: Vigorous IV saline hydration + Loop Diuretics (Furosemide) to excrete calcium. Do NOT use Thiazides.
3. Hypoparathyroidism
Pathophysiology: Inadequate PTH production → hypocalcemia.
Etiology:
Post-surgical = MCC (accidental damage/removal during thyroidectomy or parathyroidectomy).
Autoimmune destruction, radiation, heavy metal toxicity.
S&S (Neuromuscular Excitability):
Paresthesias (especially perioral numbness/tingling and fingers/toes).
Muscle cramping, spasms, tetany.
Chvostek's Sign: Tapping the facial nerve → facial muscle twitching.
Trousseau's Sign: Inflation of a BP cuff above systolic pressure for 3 minutes → carpopedal spasm.
Diagnosis (Labs):
Low Serum Ca2+, Low PTH, High Serum Phosphate.
Check Mg2+ levels (severe hypomagnesemia can inhibit PTH release).
Treatment:
Acute Tetany (Emergency): IV Calcium Gluconate and ensure patent airway.
Chronic Maintenance: Oral Calcium supplements + active Vitamin D (Calcitriol).
4. Hyperthyroidism (Thyrotoxicosis)
Causes:
Graves' Disease (MC). AI disorder caused by TSH-receptor antibodies (TSI) that stimulate the thyroid.
Toxic Multinodular Goiter (Plummer Disease).
Toxic Adenoma.
Classic Signs & Symptoms:
Heat intolerance, weight loss despite increased appetite, palpitations, tachycardia, tremors, anxiety, hyperreflexia, frequent bowel movements.
Graves' Specific: Exophthalmos (proptosis/bulging eyes), Pretibial Myxedema (non-pitting edema of lower legs), diffuse goiter with a bruit.
Diagnosis:
Low TSH, High Free T4/T3.
Thyroid Stimulating Immunoglobulins (TSI) Abs → + in Graves'.
Radioactive Iodine Uptake (RAIU) Scan:
Diffuse, homogeneous high uptake = Graves'.
Patchy uptake = Toxic Multinodular Goiter.
Focal "hot" nodule = Toxic Adenoma.
Treatment:
Symptom Control: Beta-blockers (Propranolol).
Antithyroid Drugs (Thioamides):
Methimazole: Preferred in most patients (less hepatotoxic).
Propylthiouracil (PTU): Preferred in the first trimester of pregnancy and during thyroid storm.
Definitive: Radioactive Iodine Ablation (most common in US) or Surgical Thyroidectomy.
Complication - Thyroid Storm:
Presentation: Life-threatening hypermetabolic state (high fever, severe tachycardia, delirium, vomiting/diarrhea).
Treatment: Propranolol (1st), PTU (2nd), Iodine (Lugol's - must be given 1 hour AFTER PTU to prevent Wolff-Chaikoff effect), and IV Glucocorticoids (Hydrocortisone).
5. Hypothyroidism & Thyroiditis
Hypothyroidism
Causes:
Hashimoto's Thyroiditis = MCC in the US (autoimmune destruction).
Iodine Deficiency: MCC worldwide.
Iatrogenic (post-surgical or post-radioactive iodine).
Signs & Symptoms: Cold intolerance, weight gain, fatigue, bradycardia, delayed deep tendon reflexes (DTRs), dry skin, constipation, coarse hair, non-pitting edema (myxedema).
Diagnosis:
High TSH, Low Free T4 (Primary hypothyroidism).
Antibodies: Anti-TPO (Thyroid Peroxidase) and Anti-Tg (Thyroglobulin).
Treatment:
Levothyroxine (Synthroid): Synthetic T4.
Monitoring: Recheck TSH levels every 4-6 weeks when adjusting doses until euthyroid, then annually. Take in the morning on an empty stomach.
Complication - Myxedema Coma: Severe, life-threatening hypothyroidism presenting with hypothermia, hypoventilation, AMS, and hypotension. Treat with IV Levothyroxine and passive rewarming.
Other Types of Thyroiditis
Subacute Thyroiditis:
Post-viral infection
Presents with a painful, tender thyroid gland, fever, and high ESR/CRP.
Often biphasic (transient hyperthyroidism followed by hypothyroidism).
Treat with NSAIDs (Aspirin/Ibuprofen); no antithyroid meds needed.
Infectious (Suppurative) Thyroiditis:
Bacterial origin; painful, erythematous, fluctuant neck mass with high fever.
Treat with Antibiotics and drainage.
Postpartum Thyroiditis:
Painless autoimmune thyroiditis occurring within 1 year of delivery.
Similar triphasic course as subacute, but non-tender.
6. Thyroid Nodules
Presentation: Palpable firm, nontender nodule in the thyroid. Often asymptomatic, but may cause neck discomfort, dysphagia (difficulty swallowing), or hoarseness (if compressing the recurrent laryngeal nerve).
Evaluation Algorithm:
First step: Physical Exam and TSH Level.
If TSH is LOW (Hyperthyroid state): Order a Thyroid Radionuclide Scan.
Hot Nodule: Almost always benign.
Cold Nodule: Increased risk of malignancy. Needs FNA.
If TSH is NORMAL or HIGH: Order a Thyroid Ultrasound.
Findings suspicious for cancer: Solid nodule, hypoechoic, irregular margins, microcalcifications.
FNA Biopsy: The most accurate diagnostic tool. Indicated for any suspicious nodule on ultrasound or a "cold" nodule on a scan.
7. Neoplastic Disease (Thyroid Carcinomas)
General Management: Surgical resection (Total vs. Partial Thyroidectomy) followed by Oncology consult. PET whole-body scan used for staging/metastasis check.
The 4 Main Types of Thyroid Carcinoma:
Adrenal Disorders
1. Adrenal Gland Anatomy & Physiology
Adrenal Cortex (Outer)
Produces steroid hormones; Layers from outside → inside: "GFR" (Salt, Sugar, Sex)
Zona Glomerulosa: Produces Mineralocorticoids (Aldosterone). Regulates blood pressure, retains sodium, excretes potassium.
Zona Fasciculata: Produces Glucocorticoids (Cortisol). Regulates metabolism, responds to stress, acts as an anti-inflammatory.
Zona Reticularis: Produces Androgens (DHEA, Testosterone precursors). Regulates secondary sex characteristics.
Adrenal Medulla (Inner)
Produces Catecholamines (Epinephrine and Norepinephrine). Responsible for the "fight or flight" sympathetic nervous system response.
2. Cushing Syndrome (Hypercortisolism)
Pathophysiology: Result of prolonged exposure to elevated levels of excessive glucocorticoids (cortisol).
Etiologies:
Exogenous = MCC; Due to long-term high-dose corticosteroid therapy.
Cushing's Disease = MC endogenous cause; ACTH-secreting pituitary adenoma.
Adrenal Tumor: Cortisol-secreting adenoma or carcinoma of the adrenal cortex (ACTH independent).
Ectopic ACTH: ACTH secreted by a non-pituitary tumor (classically SCLC).
Signs & Symptoms:
General: Central (truncal) obesity, "moon facies," "buffalo hump" (supraclavicular fat pads), weight gain.
Skin: Purple striae (stretch marks), easy bruising, thin skin, hyperpigmentation (only if ACTH is high).
MSK: Proximal muscle weakness, osteoporosis.
Metabolic/Cardio: Hypertension, hyperglycemia (glucose intolerance), hypokalemia.
Reproductive: Hirsutism, oligomenorrhea/amenorrhea.
Diagnosis (Stepwise Approach):
Confirm Hypercortisolism (Screening):
Initial: Low-dose Dexamethasone suppression test (normal response is suppression; Cushing's fails to suppress).
24-hour urine free cortisol (elevated).
Late-night salivary cortisol (elevated).
Determine the Cause (Once confirmed):
Check Baseline ACTH:
Low ACTH: Adrenal tumor (Negative feedback is working; order CT/MRI abdomen).
Normal/High ACTH: ACTH-dependent (Pituitary or Ectopic).
High-Dose Dexamethasone Suppression Test:
Suppresses Cortisol: Cushing's Disease (Pituitary adenoma is partially responsive to negative feedback).
Fails to Suppress Cortisol: Ectopic ACTH tumor (Lung cancer does not care about negative feedback).
Treatment:
Exogenous: Gradual tapering of corticosteroids.
Pituitary (Cushing's Disease): Transsphenoidal surgery.
Adrenal/Ectopic Tumors: Surgical resection of the tumor.
3. Adrenal Insufficiency
Primary Adrenal Insufficiency (Addison's Disease)
Definition: Destruction or dysfunction of the entire adrenal cortex. Both glucocorticoids and mineralocorticoids are deficient.
Causes:
Autoimmune = MCC in the US.
Infectious: TB = MC worldwide, HIV, fungal infections.
Vascular (hemorrhage/thrombosis), metastatic disease.
Signs & Symptoms:
Chronic fatigue, generalized weakness, anorexia, weight loss, GI symptoms (nausea/vomiting/abdominal pain).
Hyperpigmentation = Pathognomonic for primary.
Salt craving, orthostatic hypotension (due to lack of aldosterone).
Diagnosis:
Baseline Labs: Hyponatremia, Hyperkalemia, Hypoglycemia.
Screening: 8 AM plasma cortisol (low) with elevated ACTH.
Gold Standard Confirm: Cosyntropin (Synthetic ACTH) Stimulation Test. In Addison's, the adrenal glands are destroyed and fail to produce cortisol even when stimulated.
Treatment: Lifelong Glucocorticoids (Hydrocortisone) AND Mineralocorticoids (Fludrocortisone).
Secondary Adrenal Insufficiency
Definition: Pituitary failure of ACTH secretion.
Causes: Exogenous steroid withdrawal = MC, pituitary adenomas, Sheehan syndrome, head trauma.
Key Differences from Primary:
Aldosterone is intact (NO severe hyperkalemia or hyponatremia).
ACTH is low, so NO hyperpigmentation.
Treatment: Glucocorticoids (Hydrocortisone) only.
4. Acute Adrenal Crisis (Addisonian Crisis)
Trigger: Stressful event (infection, trauma, surgery) in a patient with Addison's, or abrupt withdrawal of long-term glucocorticoids.
Signs & Symptoms:
Shock: Severe hypotension that is refractory to vasopressors/fluids.
Acute abdominal pain, intractable vomiting, fever, AMS, coma.
Treatment (Medical Emergency):
Do NOT wait for lab results to treat.
Immediate IV Hydrocortisone (Stress dose).
Aggressive IV normal saline resuscitation.
Correct hypoglycemia and electrolyte imbalances.
5. Aldosterone Disorders
Primary Hyperaldosteronism (Conn's Syndrome)
Causes: Bilateral idiopathic adrenal hyperplasia = MC or an Aldosterone-secreting adenoma (Conn's syndrome).
Signs & Symptoms:
Refractory Hypertension: Often severe and resistant to multiple blood pressure meds.
Hypokalemia: Leading to muscle weakness, cramps, polyuria, and polydipsia.
Diagnosis:
High Aldosterone, Low Renin. (Aldosterone-to-Renin Ratio > 20:1).
Saline infusion test (aldosterone stays high).
CT/MRI of the abdomen to look for adenoma vs hyperplasia.
Treatment:
Hyperplasia: Aldosterone antagonists (Spironolactone or Eplerenone).
Adenoma: Surgical resection (Adrenalectomy).
Hypoaldosteronism
Causes: Diabetic nephropathy, ACE inhibitors, ARBs, NSAIDs, Addison's disease.
Labs: Hyperkalemia, Hyponatremia.
6. Pheochromocytoma
Pathophysiology: A rare, catecholamine-secreting tumor of the chromaffin cells of the adrenal medulla (secretes Norepinephrine and Epinephrine).
Signs & Symptoms (The Classic Triad - "PHE"):
Palpitations
Headache (severe, pounding)
Excessive sweating (diaphoresis)
Also: Severe paroxysmal (episodic) hypertension, anxiety, tremors.
Diagnosis:
Biochemical: 24-hour urine fractionated metanephrines and catecholamines. Plasma free metanephrines.
Imaging: CT or MRI of the abdomen/pelvis to locate the tumor.
Treatment & Crucial Pre-Op Management:
Definitive treatment is surgical resection of the tumor.
CRITICAL RULE: Must administer an Alpha-blocker (e.g., Phenoxybenzamine or Phentolamine) for 1-2 weeks BEFORE starting a Beta-blocker (e.g., Propranolol).
Why? If beta-blockade is started prematurely, unopposed alpha-receptor stimulation by the catecholamines will cause severe, life-threatening vasoconstriction and hypertensive crisis.
7. High-Yield Cortisol / ACTH Lab Patterns Summary
Male Endo Disorders & MEN
Male Endocrine Disorders (Hypogonadism)
Hypogonadotropic Hypogonadism (Secondary)
Pathophysiology: The problem lies in the brain (Hypothalamus or Pituitary). The brain fails to secrete sufficient GnRH, FSH, or LH to stimulate the testes.
Lab Profile: LOW Testosterone, accompanied by LOW or inappropriately NORMAL FSH and LH.
Causes:
Pituitary or hypothalamic tumors.
Suppression by severe illness, stress, extreme exercise, or malnutrition.
Medications (Opioids, high-dose glucocorticoids).
Kallmann Syndrome: Congenital GnRH deficiency.
Classic presentation is delayed puberty accompanied by anosmia (inability to smell).
Hypergonadotropic Hypogonadism (Primary)
Pathophysiology: The problem lies in the testes themselves (testicular failure). The testes cannot produce testosterone or sperm despite being strongly stimulated by the brain.
Lab Profile: LOW Testosterone, accompanied by HIGH FSH and LH (due to the lack of negative feedback from testosterone).
Causes:
Klinefelter Syndrome = MC congenital cause.
Presents with tall stature, small/firm testes, gynecomastia, and infertility.
Viral infections (Mumps orchitis).
Trauma, radiation, chemotherapy.
Autoimmune destruction.
Clinical Presentation of Testosterone Deficiency
Pre-pubertal onset: Delayed or absent puberty, lack of secondary sex characteristics (voice deepening, body hair), eunuchoid proportions (arms/legs longer than torso).
Post-pubertal onset: Decreased libido, erectile dysfunction, loss of morning erections, fatigue, depression, decreased muscle mass, increased body fat, osteopenia/osteoporosis.
Evaluation & Diagnosis
Screening: Morning (8 AM - 10 AM) total serum testosterone. (Levels are highest in the morning; must be confirmed with a second early-morning level if low).
Workup: If testosterone is confirmed low, check FSH and LH to distinguish between primary (high FSH/LH) and secondary (low FSH/LH).
Treatment & Management
Testosterone Replacement Therapy (TRT): Given via injections, transdermal gels/patches, or pellets.
Contraindications: Prostate cancer, breast cancer, severe lower urinary tract symptoms (BPH), uncontrolled heart failure, severe untreated sleep apnea, or a hematocrit > 50%.
Monitoring: Must routinely check digital rectal exam (DRE), PSA levels, and CBC (watching for erythrocytosis/polycythemia).
Risks of Anabolic Steroid Abuse: Exogenous testosterone suppresses natural LH/FSH production, leading to profound testicular atrophy and infertility. It also causes dyslipidemia, hypertension, mood swings ("roid rage"), and hepatotoxicity.
Multiple Endocrine Neoplasia (MEN) Syndromes
MEN Type 1 (Wermer's Syndrome)
Genetics: Mutation in the MEN1 gene.
The "3 P's":
Parathyroid: Hyperparathyroidism (present in >90% of cases). Usually the first clinical sign. Due to multi-gland hyperplasia.
Pancreatic (Islet Cell) Tumors: (54%).
Gastrinoma (Zollinger-Ellison syndrome) - causes severe, refractory peptic ulcers.
Insulinoma - causes severe hypoglycemia.
Pituitary Adenomas: (42%).
Prolactinoma = MC
Screening/Labs: Serum calcium, intact PTH, prolactin, fasting gastrin, fasting glucose/insulin.
MEN Type 2A (Sipple's Syndrome)
Genetics: Mutation in the RET proto-oncogene.
The "2 P's & 1 M":
Medullary Thyroid Carcinoma (MTC): (>90%). Almost always occurs; often bilateral and multicentric. Secretes Calcitonin.
Pheochromocytoma: (20-50%). Tumor of the adrenal medulla secreting catecholamines (causes episodic hypertension, headaches, palpitations). Often bilateral.
Parathyroid Hyperplasia: (20-50%). Leading to hypercalcemia.
Screening/Labs: RET germline mutation testing, plasma calcitonin, plasma free metanephrines / 24-hour urine catecholamines, serum calcium.
MEN Type 3 (Formerly MEN 2B)
Genetics: Also a mutation in the RET proto-oncogene.
Clinical Features (1 P, 2 M's, + Phenotype):
Medullary Thyroid Carcinoma (MTC): (90%). Tends to be more aggressive and present earlier than in 2A.
Pheochromocytoma: (60%).
Marfanoid Habitus: Tall, long extremities, hypermobile joints.
Mucosal Neuromas: Bumpy, benign nerve tumors on the lips, tongue, and eyelids.
Intestinal Ganglioneuromas: (>90%). Can cause GI issues/constipation.
Key Difference from 2A: Parathyroid disease is rare in MEN 2B.
Screening/Labs: RET testing, serum calcitonin, plasma free metanephrines.
MEN Type 4
Genetics: No mutation in the menin or RET genes. Involves mutations in CDK inhibitors (like CDKN1B).
Clinical Features: Very similar clinical picture to MEN 1.
Parathyroid tumors (common).
Pituitary tumors (common).
Pancreatic tumors (common).
Thyroid adenomas (common).
High-Yield Summary Table: MEN Syndromes
Medical Interventions: Hormone Therapy
Feminizing Hormone Therapy (Transgender Women)
Goal: Suppress endogenous testosterone and introduce estrogen to induce feminization.
Medications:
Estrogen: 17-beta estradiol is preferred (oral, transdermal, or injectable). Avoid ethinyl estradiol due to high DVT/VTE risk.
Anti-androgens:
Spironolactone = Most commonly used in the US.
Cyproterone acetate (not FDA approved in the US)
GnRH agonists (Leuprolide); highly effective but very expensive.
Expected Changes: Breast development, redistribution of body fat, decreased muscle mass, softening of skin, decreased terminal hair growth, decreased spontaneous erections/testicular volume.
Monitoring: Routinely check Estradiol levels and Testosterone levels
Masculinizing Hormone Therapy (Transgender Men)
Goal: Introduce testosterone to induce masculinization and suppress endogenous estrogen production.
Medications:
Testosterone: Typically administered via IM/SubQ injections or transdermal gels/patches.
Expected Changes: Deepening of voice (irreversible), clitoral enlargement (irreversible), facial and body hair growth (irreversible), cessation of menses (amenorrhea), increased muscle mass, redistribution of fat.
Monitoring: Routinely check total Testosterone levels (aiming for normal male physiologic range), CBC (specifically monitoring Hematocrit/Hemoglobin for erythrocytosis/polycythemia), and lipid panels.