ENDO Flashcards
1
Q
What are the effects of underproduction and overproduction in pituitary space-occupying lesions?
A
Underproduction: Causes hypopituitarism. Overproduction: GH excess → Gigantism (before epiphysis fusion) or acromegaly (after epiphysis fusion). Prolactin excess → Galactorrhea, amenorrhea, erectile dysfunction. ACTH excess → Cushing’s disease. TSH excess → Hyperthyroidism.
2
Q
Are pituitary tumors typically benign or malignant, and what are the associated symptoms?
A
Almost all pituitary tumors are benign (mostly adenoma). They may grow in various directions causing ‘parasellar’ signs and symptoms.
3
Q
What are the local effects of pituitary tumors?
A
- Optic chiasm: Bitemporal hemianopia. - Cavernous sinus: Cranial nerve III, IV, VI lesions. - Bone and meninges: Headache. - Hypothalamic centers: Obesity, altered appetite & thirst, precocious puberty. - Ventricles: CSF flow interruption → Hydrocephalus.
4
Q
How are pituitary mass lesions typically diagnosed?
A
MRI is the imaging study of choice, and other rarer causes like craniopharyngioma, secondary deposits, sarcoidosis, or Wegner’s should be ruled out.
5
Q
What is an incidentaloma, and how is it managed?
A
Incidentaloma: A pituitary tumor found in asymptomatic patients. Management: Microadenoma (<1 cm): Check prolactin levels and perform yearly MRI. Macroadenoma (>1 cm): Check prolactin levels, TSH, T4, LH, FSH, IGF; yearly MRI and visual field testing for optic chiasm compression.
6
Q
What are the treatment options for pituitary tumors?
A
- Transsphenoidal surgery: Primary treatment for most patients (except prolactinomas medical tx first). 2. Radiation therapy and medical therapy: Often used as adjuncts.
7
Q
What are the common causes of hypopituitarism?
A
Pituitary or hypothalamic tumors (most common cause, leading to compression and necrosis). Previous surgery/radiation for pituitary adenoma. Sheehan syndrome, infiltrative processes (e.g., sarcoidosis, hemochromatosis), head trauma, cavernous sinus thrombosis.
8
Q
What are the clinical features of hypopituitarism based on the affected hormone?
A
GH deficiency: Short stature in children, silent in adults, increased LDL, risk of heart disease. LH & FSH deficiency: Loss of libido, amenorrhea, erectile dysfunction. ACTH deficiency: Hypotension (secondary adrenal insufficiency). TSH deficiency: Fatigue and tiredness (secondary hypothyroidism). Prolactin deficiency: Failure to lactate. ADH deficiency: Diabetes insipidus. MSH deficiency: Decreased skin and hair pigmentation. Long-standing hypopituitarism: Pallor with hairlessness (alabaster skin).
9
Q
What syndromes are associated with hypopituitarism?
A
Kallmann’s syndrome: Congenital GnRH deficiency with anosmia. Sheehan’s syndrome: Postpartum hemorrhage leading to pituitary infarction (empty sella tunica on imaging). Pituitary apoplexy: Rapid tumor size increase due to infarction or hemorrhage. Empty sella syndrome: Primary (enlargement of sella tunica -> CSF leak causes compression); Secondary (small pituitary due to post-surgery or increased ICP).
10
Q
How is hypopituitarism diagnosed and treated?
A
Diagnosis: Low target hormone levels with low/normal trophic hormones, MRI of the brain. Treatment: Hormone supplementation based on the deficient hormone.
11
Q
What are the causes of hyperprolactinemia?
A
Pathological causes: Pituitary adenoma (prolactinoma), primary hypothyroidism, acromegaly, PCOS, certain drugs (e.g., antipsychotics, opioids), suprasellar mass lesions. Physiological causes: Pregnancy, intense exercise, renal insufficiency, increased chest wall stimulation.
12
Q
What are the clinical features of hyperprolactinemia?
A
General: Galactorrhea, headaches, visual field defects (macroadenomas). Females: Amenorrhea, infertility, decreased libido, vaginal dryness, risk of osteoporosis. Males: Erectile dysfunction, decreased libido, infertility.
13
Q
How is hyperprolactinemia diagnosed and treated?
A
Diagnosis: Serum prolactin, TFT, pregnancy test, BUN/creatinine, LFT, and MRI of the pituitary. Tx: Medical: Dopamine agonists (cabergoline, bromocriptine). Surgical: Transsphenoidal resection if unresponsive to medications. Asymptomatic cases do not require treatment.
14
Q
What is the basic physiology of growth hormone?
A
Stimulated by: GHRH, Ghrelin. Inhibited by: somatostatin. Directly acts on liver, muscles, fat and bone or indirectly by IGF-1.
15
Q
What is the difference between acromegaly and gigantism?
A
Acromegaly: GH excess after epiphyseal closure. Gigantism: GH excess before epiphyseal closure.
16
Q
What causes acromegaly and gigantism?
A
GH-secreting pituitary adenoma (most common). Associated with MEN 1 (when combined with parathyroid, pancreatic disorders). Rarely, ectopic GH/GHRH production (lymphoma, bronchial carcinoid).
17
Q
What are the symptoms of acromegaly due to local mass effects?
A
Headaches, bitemporal hemianopia (optic chiasm compression), cavernous sinus involvement (lateral growth), sphenoid sinus invasion (inferior growth), damage to pituitary stalk (hyperprolactinemia) and hypopituitarism (decrease in pituitary hormones due to infarction of pituitary gland).
18
Q
What are the systemic symptoms of acromegaly?
A
Enlargement of extremities, spade-like hands, increase in ring/hat/shoe size. Coarsening of facial features, prominent supraorbital ridges, prognathism, macroglossia, dental spacing. Carpal tunnel syndrome, arthralgias. Hyperhidrosis, body odor due to sweat gland hypertrophy. Acanthosis nigricans and skin tags. Hypertrophic cardiomyopathy (most common cause of death in acromegaly). Hypertension resistant to treatment, CHF. Hyperglycemia, hyperphosphatemia, hypercalciuria, hypertriglyceridemia. Increased incidence of colonic polyps and risk of colon cancer. Erectile dysfunction.
19
Q
How is acromegaly diagnosed?
A
Serum IGF-1. Oral glucose suppression test. MRI of the pituitary area. Serum prolactin level. Laboratory findings: Glucose intolerance, hyperlipidemia (both contribute to cardiac dysfunction).
20
Q
How is acromegaly treated?
A
Primary treatment: Transsphenoidal resection of the pituitary adenoma (70% of patients respond). Cabergoline, octreotide, pegvisomant. Radiation therapy: Reserved for cases unresponsive to surgery and medications.
21
Q
What is Conn’s Syndrome?
A
Primary hyperaldosteronism due to autonomous overproduction of aldosterone from the adrenal cortex, typically caused by an adrenal adenoma. Causes: 80% from solitary adenoma. Remaining cases from bilateral hyperplasia of adrenal glands or rarely malignant.
22
Q
What is the pathophysiology of Conn’s Syndrome?
A
Excess mineralocorticoids increase Na+/K+ pump activity in the cortical collecting tubules: Sodium retention → extracellular fluid (ECF) volume expansion and hypertension. Potassium loss → hypokalemia.
23
Q
What are the clinical features of Conn’s Syndrome?
A
Hypertension: Common under age 30 or over 60, resistant to 3 antihypertensive drugs (5-10% of all HTN). Hypokalemia: → Muscle weakness. Diabetes insipidus: Polyuria, nocturnal polyuria (hypokalemia has negative effect on ADH). Metabolic alkalosis: From increased hydrogen ion secretion. Key Sign: High BP + hypokalemia indicates primary hyperaldosteronism.
24
Q
How is Conn’s Syndrome diagnosed?
A
Initial investigations: Discontinue medications affecting results (BB, ACE inhibitors, ARBs, spironolactone). Plasma aldosterone: renin ratio: Best initial test (ratio >20:1 with aldosterone >15). Confirmatory tests: Plasma renin: Low levels. Exclude Conn’s if high renin. Normal saline infusion test: Most accurate test; aldosterone levels fail to suppress. Oral sodium loading: High urinary aldosterone with high urinary sodium confirms diagnosis. Imaging: CT/MRI of adrenals to differentiate adenoma from hyperplasia. Adrenal venous sampling: Confirms unilateral adenoma vs. bilateral hyperplasia.
25
How is Conn’s Syndrome treated?
Surgical: Removal of the unilateral adenoma. Medical: Eplerenone or spironolactone for bilateral hyperplasia or patients unfit for surgery. Hypertension management: Spironolactone is effective.
26
What is adrenal insufficiency, and how is it classified?
Primary adrenal insufficiency (Addison disease): Destruction of the entire adrenal cortex, leading to deficiencies in glucocorticoids, mineralocorticoids, and sex steroids. Secondary adrenal insufficiency: Due to chronic suppression of CRH and ACTH by exogenous steroids or hypopituitarism. Tertiary adrenal insufficiency: Hypothalamic disease.
27
What are the causes of primary adrenal insufficiency?
Autoimmune diseases (most common). Infectious diseases (e.g., tuberculosis, fungal infections, cytomegalovirus). Metastatic disease (lung or breast cancer). Hemorrhage or infarction (e.g., meningococcal septicemia). Genetic causes (e.g., adrenoleukodystrophy). Iatrogenic: e.g., bilateral adrenalectomy. Infiltration: amyloid and malignant metastasis. Polyglandular autoimmune syndromes (associated with other autoimmune diseases like type 1 DM).
28
What are the features due to lack of cortisol?
Fatigue, weakness, and weight loss. Hypoglycemia. Nausea, vomiting, and abdominal pain. Lethargy, confusion, and possible psychosis. Hyperpigmentation (only in primary adrenal insufficiency) Pigmentations (grey-brown): palmar creases and buccal area.
29
What are the features due to low aldosterone (only in primary adrenal insufficiency)?
Hypotension. Hyponatremia. Hyperkalemia. Metabolic acidosis. Salt craving.
30
What are the clinical features of acute adrenal crisis, how to manage?
Profound hypotension, fever, confusion, coma. Tx: IV hydrocortisone and IV fluids 5% dextrose.
31
How is adrenal insufficiency diagnosed?
Tests for cortisol: Plasma cortisol. ACTH stimulation test (Cosyntropin test). ACTH levels: High ACTH with low cortisol → Primary adrenal insufficiency. Low ACTH with low cortisol → Secondary adrenal insufficiency. Additional tests: Plasma renin activity: high. Lab finding: hyponatremia, hypoglycemia, hyperkalemia, metabolic acidosis, high BUN. Adrenal antibodies (e.g., 21-hydroxylase antibodies). Imaging: MRI for pituitary/hypothalamus, CT for adrenal glands.
32
How is adrenal insufficiency treated?
Acute adrenal crisis: IV fluids (0.9% saline) with IV hydrocortisone (100 mg bolus, then every 6 hours till stabilize). Glucose infusion if hypoglycemic. Fludrocortisone started before discharge. Long-term management: Primary AI: Daily oral hydrocortisone/prednisone & fludrocortisone. Secondary AI: Only glucocorticoid replacement is necessary.
33
What is Cushing syndrome, and how does it differ from Cushing disease?
Cushing syndrome: Results from excess cortisol due to any cause (e.g., exogenous steroids, adrenal adenomas). Cushing disease: Results from pituitary overproduction of ACTH (e.g., pituitary adenoma).
34
What are the causes of Cushing syndrome?
Iatrogenic: Most common, due to long-term steroid use. ACTH-dependent causes: Pituitary adenoma (Cushing disease), ectopic ACTH secretion (thymoma/bronchial carcinoid/small cell lung carcinoma). ACTH-independent causes: Adrenal adenomas or carcinomas.
35
What are the clinical features of Cushing syndrome?
Fat redistribution: Moon face, dorsocervical fat pad , central obesity, thin extremities. Skin changes: Purple striae, hirsutism, acne, easy bruising, delayed wound healing & thinning of skin. Muscle and bone issues: Proximal muscle weakness, osteoporosis, aseptic necrosis of the femoral head. Metabolic changes: Hyperglycemia, diabetes, polyuria, hypokalemia, metabolic alkalosis. Psychological effects: Depression, cognitive impairment, psychosis. Menstrual irregularity, erectile dysfunction & infertility. Masculinization in females (in ACTH-dependent forms) from androgen excess. HTN
36
How is Cushing syndrome diagnosed?
Confirm cortisol excess: 24-hour urinary free cortisol (elevated). 1 mg overnight dexamethasone suppression test (cortisol >5 confirms Cushing, >5-10 determine what is the cause). Midnight salivary cortisol (elevated). Establish the cause: ACTH levels: Low → Adrenal source. High → Pituitary or ectopic source. High-dose dexamethasone suppression test: Suppressed → Pituitary adenoma (Cushing disease). Not suppressed → Ectopic ACTH secretion.
37
How is Cushing syndrome treated?
Iatrogenic Cushing syndrome: tapering of glucocorticoid. Pituitary adenoma (Cushing disease): Transsphenoidal surgery. Adrenal adenoma or carcinoma: Surgical resection. Ectopic ACTH production: Treat the underlying tumor. Medical therapy: Somatostatin analogs if surgery is not possible.
38
What is hypothyroidism?
Underactivity of the thyroid gland. Types: Primary: Issues with the thyroid gland itself (95% of cases). Secondary: Due to pituitary disease (low TSH). Tertiary: Due to hypothalamic disease (low TRH). Secondary and tertiary forms are associated with low free T4 and low TSH.
39
What are the causes of hypothyroidism?
Primary hypothyroidism: Hashimoto’s thyroiditis (most common cause): Autoimmune destruction of thyroid tissue. Iatrogenic: Following thyroidectomy, radioactive iodine therapy, or external neck irradiation. De Quervain’s thyroiditis (subacute viral thyroiditis): Painful, tender thyroid gland following viral illness.
40
What are the causes of hypothyroidism?
Primary hypothyroidism: Hashimoto’s thyroiditis (most common cause), Iatrogenic, De Quervain’s thyroiditis, Drug-induced, Iodine deficiency, Congenital hypothyroidism, Post-partum hypothyroidism.
41
What are the antibodies associated with Hashimoto's thyroiditis?
Abs against Thyroglobulin, thyroid peroxidase enzyme, abs blocking TSH binding to its receptor.
42
What are the signs and symptoms of hypothyroidism?
Tiredness, malaise, fatigue, depression, weight gain, cold intolerance, bradycardia, dry brittle hair, dry skin, loss of lateral 1/3 of eyebrow, periorbital edema, slow-relaxing reflexes, menorrhagia, constipation, proximal myopathy, carpal tunnel syndrome, goiter, diastolic hypertension, diminished hearing.
43
What is Subclinical hypothyroidism?
High TSH with normal T4.
44
How is hypothyroidism diagnosed?
TSH: High in primary hypothyroidism, low in secondary or tertiary hypothyroidism. Serum free T4: Low. Additional tests: Thyroid antibodies, blood work for anemia, hypercholesterolemia, hypertriglyceridemia, hyponatremia, high CK, LDH, AST.
45
How is hypothyroidism managed?
Medication: Lifelong levothyroxine at 1.6 mcg/kg/day. Monitoring: TSH assessed 6 weeks after initiating or adjusting dose. Goal: Normalize TSH levels.
46
What is Euthyroid Sick Syndrome?
A condition where patients with non-thyroidal systemic illness have abnormal thyroid hormone levels but no intrinsic thyroid disease.
47
What is the pathophysiology of Euthyroid Sick Syndrome?
Multifactorial and not fully understood. Key mechanisms: Altered deiodinase activity, cytokines affecting TSH and thyroid hormone levels, protein loss decreasing thyroid-binding globulin levels.
48
How is Euthyroid Sick Syndrome diagnosed and managed?
Diagnosis: Normal or low TSH with low T3 and high rT3. Management: Treat the underlying systemic illness.
49
What are the causes of hyperthyroidism?
Graves’ disease, Toxic multinodular goiter, Solitary toxic adenoma, De Quervain’s thyroiditis, Postpartum thyroiditis, Exogenous thyroid hormone use, Pituitary adenoma.
50
What are the clinical features of hyperthyroidism?
Weight loss, heat intolerance, anxiety, restlessness, tremor, diarrhea, sweating, tachycardia, palpitations, oligomenorrhea, lid lag, goiter, hyperreflexia, systolic hypertension.
51
What signs are specific to Graves’ disease?
Exophthalmos, ophthalmoplegia, pretibial myxedema, thyroid bruit, thyroid acropachy.
52
How is hyperthyroidism diagnosed?
Lab tests: Low TSH, high free T4 and/or T3. Imaging: Thyroid ultrasound or radionuclide scan.
53
What are lab electrolytes seen in hyperthyroidism?
Hypokalemia, hypercalcemia, hypoalbuminemia.
54
What are antibodies seen in hyperthyroidism?
Anti-thyroglobulin, Thyroid stimulating immunoglobulin (TSI), Thyroid stimulating hormone receptor ab (TRAb), Anti-Thyroperoxidase ab (TPO).
55
How is hyperthyroidism managed?
Medical treatment: Antithyroid drugs, beta-blockers, steroids, radiotherapy, surgical treatment.
56
What is thyroid storm, and what are its precipitating factors?
Life-threatening complication of thyrotoxicosis with end-organ damage. Precipitating factors: Infection, DKA, severe trauma, surgery, illness, childbirth.
57
What are the clinical features of thyroid storm?
Fever, tachycardia, arrhythmias, agitation, confusion, GI symptoms.
58
How is thyroid storm treated?
Supportive care, address thyroid hormone excess, identify and treat precipitating illness.
59
What are the risks of uncontrolled hypothyroidism during pregnancy?
Impaired fetal neurocognitive development, increased risk of preterm birth, low birth weight, pregnancy loss, lower offspring IQ.
60
What are the risks of uncontrolled hyperthyroidism during pregnancy?
Pregnancy loss, pregnancy-induced hypertension, preterm birth, low birth weight, stillbirth, intrauterine growth restriction.
61
How do thyroid hormone levels change during pregnancy?
hCG stimulates the thyroid, increasing thyroid hormone production; estrogen increases thyroid-binding globulin, decreasing free thyroid hormones.
62
What are the treatment goals for thyroid hormone in pregnancy?
Normalize TSH to trimester-specific ranges: First trimester: 0.1–2.5 mIU/L, Second trimester: 0.2–3.0 mIU/L, Third trimester: 0.3–3.0 mIU/L.
63
How is hypothyroidism managed during pregnancy?
Increase levothyroxine dose by 25–30% as early as 4–6 weeks of gestation. Monitor TSH every 4–6 weeks.
64
What are the risks of Graves’ disease during pregnancy?
Fetal or neonatal hyperthyroidism, fetal or neonatal hypothyroidism, central hypothyroidism.
65
How is Graves’ disease managed during pregnancy?
TRAb monitoring, antithyroid drugs: Use PTU in the first trimester, switch to methimazole in the second and third trimesters.
66
Function of PTH?
Increases calcium (kidney reabsorption, bone resorption, vitamin D activation), decreases phosphate (renal excretion).
67
Function of vitamin D?
Increases both calcium and phosphate absorption.
68
Causes of hypoparathyroidism?
Surgical: Thyroidectomy, parathyroidectomy, radical neck surgery. Non-surgical (rare): Autoimmune, congenital.
69
Causes of hyperparathyroidism?
Primary: Adenoma (85%), hyperplasia (15%), carcinoma (1%) (may be associated with MEN syndrome). Secondary: Chronic kidney disease, vitamin D deficiency, renal hypercalciuria. Tertiary: Long-standing CKD with autonomous PTH secretion.
70
Symptoms of hypoparathyroidism?
Hypocalcemia signs: Tetany, numbness, grand mal seizures, arrhythmias, rickets & osteomalacia. Neuromuscular: Chvostek sign (facial twitching), Trousseau sign (carpal spasm with BP cuff). Other: Cataracts, basal ganglia calcifications, stridor.
71
Symptoms of hyperparathyroidism?
Stones: Kidney stones, nephrocalcinosis. Bones: Bone pain, osteoporosis, osteitis fibrosa cystica. Groans: Muscle weakness, pancreatitis, peptic ulcer, gout, constipation. Psychiatric Overtones: Depression, fatigue, anorexia, sleep disturbances, anxiety, lethargy. Other: Polydipsia, polyuria, hypertension, weight loss.
72
Diagnosis of hypoparathyroidism?
Labs: Low calcium, high phosphate, low PTH. Urine: Low urine cAMP. ECG: Long QT (prolonged repolarization).
73
Diagnosis of hyperparathyroidism?
Labs: High calcium, high PTH, low phosphate. Urine: High urine cAMP, hypercalciuria. Renal: Elevated BUN & creatinine. ECG: Short QT. Radiology: Osteopenia (DEXA scan preferred). Chloride/phosphorus ratio > 33 (diagnostic for primary hyperparathyroidism).
74
Treatment of hypoparathyroidism?
IV calcium gluconate (severe cases), oral calcium (mild cases). Vitamin D supplementation (calcitriol). Monitor for urinary stones (due to increased urinary calcium).
75
Treatment of hyperparathyroidism?
Surgery (definitive treatment): Hyperplasia: Remove all 4 glands, reimplant small tissue in the forearm. Adenoma: Remove the adenoma (curative). Carcinoma: Remove tumor, ipsilateral thyroid lobe, and enlarged lymph nodes. Non-surgical: Cinacalcet (inhibits PTH release). Encourage fluids. Loop diuretics (furosemide) to excrete calcium (avoid thiazides as they retain calcium).
76
Definition and classification of hypercalcemia?
Calcium > 2.6 mmol/L. Corrected calcium formula: 0.02 × (40 - albumin). Severity: Mild: Up to 3 mmol/L, Moderate: 3–3.5 mmol/L, Severe: >3.5 mmol/L.
77
Causes of hypercalcemia?
Primary hyperparathyroidism (most common). Malignancy: Multiple myeloma, squamous lung, prostate, breast cancer. Tertiary hyperparathyroidism (chronic kidney disease). Vitamin D intoxication, sarcoidosis, TB. Drugs: Thiazides, lithium, vitamin A & D overdose. Endocrine: Hyperthyroidism, Addison’s disease. Milk-alkali syndrome (excess calcium carbonate intake). Familial/genetics PTH-related peptide.
78
Symptoms of hypercalcemia?
Asymptomatic: Often detected on routine blood tests. Acute severe hypercalcemia: Confusion, stupor, loss of consciousness, cardiac arrest. Stones: Nephrolithiasis, nephrocalcinosis. Bones: Bone pain, fractures, osteitis fibrosa cystica. Groans: Muscle weakness, nausea, constipation, pancreatitis. Psychiatric overtones: Depression, fatigue, anxiety, anorexia, sleep disturbances. Cardiovascular: Hypertension, bradycardia. Corneal calcification.
79
ECG findings in hypercalcemia?
Short QT interval, Prolonged QR, Wide ST segment, Bradycardia or arrhythmias.
80
Approach to diagnosing hypercalcemia?
History: Symptoms, drug use (thiazides, vitamins), family history. Labs: Calcium, PTH, vitamin D, phosphate, renal function, ACE, PTH-related peptide. High PTH: Primary or tertiary hyperparathyroidism. Low PTH: Malignancy, drugs, other causes. Urinary calcium and cAMP (elevated in primary hyperparathyroidism). ECG: Short QT, prolonged QRS, bradycardia. Radiology: Osteopenia (DEXA preferred).
81
Treatment of acute severe hypercalcemia?
Stop medications that increase calcium. IV saline hydration (4–6 L over 24 hours). Loop diuretics (furosemide) to promote calcium excretion. Calcitonin (nasal or subcutaneous) for rapid reduction in calcium. IV bisphosphonates (pamidronate, zoledronic acid) for long-term control. Steroids for cases due to MM, lymphoma, sarcoidosis, or vitamin D intoxication. Dialysis if refractory or severe (Ca > 3.5 mmol/L, LOC, arrhythmias).
82
Definition of hypocalcemia?
Serum calcium < 2.2 mmol/L. Severe if <1.9 mmol/L or symptomatic.
83
Causes of hypocalcemia?
Hypoparathyroidism (surgical, autoimmune, congenital). Vitamin D deficiency, CKD, hypomagnesemia, pancreatitis. Drugs: Bisphosphonates, calcitonin, anticonvulsants. Pseudohypoparathyroidism (end-organ resistance to PTH). DiGeorge syndrome (chromosome 22 deletion). Renal insufficiency, hyperphosphatemia, liver/renal impairment, malabsorption, secondary hyperparathyroidism, alkalemia.
84
Symptoms of hypocalcemia?
Tetany, seizures, muscle cramps. Chvostek sign, Trousseau sign. Arrhythmias, long QT.
85
Treatment of hypocalcemia?
IV calcium gluconate for severe cases. Oral calcium and vitamin D for chronic cases. Magnesium replacement if deficient.
86
What is Multiple Endocrine Neoplasia (MEN) and inheritance pattern?
A group of inherited disorders causing tumors in multiple endocrine glands. Autosomal dominant.
87
What are the types of MEN and their associated tumors?
MEN 1: Parathyroid hyperplasia, pancreatic tumors, pituitary adenomas. MEN 2A: Medullary thyroid cancer, pheochromocytoma, hyperparathyroidism. MEN 2B: Medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid habitus.
88
What is the first manifestation in MEN 1 and what do women have a higher risk of with MEN 1?
HYPERParathyroid, BREAST CANCER.
89
MEN 2 gastrointestinal symptoms?
Constipation, diarrhea, megacolon. These are a result of growing neuromas on intestinal nerves.
90
What is the treatment for MEN-related tumors?
Parathyroidectomy for hyperparathyroidism. Surgical excision of pancreatic or pituitary tumors. Thyroidectomy for MEN 2-related medullary thyroid cancer. Adrenalectomy if pheochromocytoma is present (must be treated first before thyroid surgery).
91
What is pheochromocytoma?
A rare adrenal medulla tumor that secretes excessive catecholamines (epinephrine, norepinephrine).
92
What genetic syndromes are associated with pheochromocytoma?
MEN 2A, MEN 2B, Von Hippel-Lindau (VHL), Neurofibromatosis type 1 (NF1).
93
What are the 'Rule of 10s' in pheochromocytoma?
10% extra-adrenal, 10% bilateral, 10% familial, 10% in children, 10% malignant, 10% associated with MEN syndromes.
94
What is the classic triad of pheochromocytoma symptoms?
Palpitations, throbbing headache, and paroxysmal hypertension, and sweating
95
What are triggers paraoxysmal htn in pheochromocytoma ?
Stress, surgery, beta-blockers, tyramine-rich foods (aged cheese, red wine).
96
How is pheochromocytoma diagnosed?
Biochemical tests: 24-hour urinary catecholamines/metanephrines, plasma fractionated metanephrines. Imaging: CT/MRI (first-line), MIBG scan for extra-adrenal tumors. Genetic testing for MEN 2, VHL, NF1 if suspected.
97
What is the treatment for pheochromocytoma?
Surgical excision of the tumor (laparoscopic adrenalectomy). Preparation for surgery: Alpha-blockers first (phenoxybenzamine, terazosin) to control blood pressure. Beta-blockers (only after alpha-blockade) to control tachycardia. IV fluids to prevent hypotension.
98
Why must alpha-blockers be given before beta-blockers in pheochromocytoma?
Beta-blockers alone can cause unopposed alpha-adrenergic vasoconstriction, leading to hypertensive crisis.
99
What is Polycystic Ovarian Syndrome (PCOS)?
A hormonal disorder with ovarian cysts, menstrual irregularities, and hyperandrogenism.
100
What causes PCOS?
Insulin resistance and hyperinsulinemia. Increased ovarian androgen production. Imbalance in LH and FSH. Obesity-related estrogen production.
101
What are the symptoms of PCOS?
Menstrual irregularities: Oligomenorrhea, amenorrhea. Hyperandrogenism: Hirsutism, acne, male-pattern hair loss. Obesity & metabolic issues: Insulin resistance, type 2 diabetes, acanthosis nigricans. Infertility: Due to anovulation. Psychological symptoms: Depression, anxiety.
102
What is the diagnostic criteria for PCOS?
Rotterdam Criteria (2 out of 3 must be present): Oligo/amenorrhea (irregular ovulation). Clinical or biochemical hyperandrogenism (hirsutism, acne, high testosterone/androstenedione/dehydroepiandrosterone). Polycystic ovaries on US (>12 small follicles per ovary).
103
What are the ultrasound findings in PCOS?
'String of pearls' appearance due to multiple cysts (>12 follicles, 2–9 mm in diameter).
104
What is the microscopic appearance of PCOS?
Ovarian hypertrophy with thick capsule. Stromal hyperplasia and fibrosis. Multiple enlarged cystic follicles. Hyperluteinized theca cells. Decreased granulosa cell layer.
105
What are the hormonal findings in PCOS?
High androgens: Increased testosterone, androstenedione, DHEA-S. High LH, low FSH (LH:FSH ratio ≥ 2). Slightly elevated prolactin.
106
What are complications of PCOS?
Metabolic: Type 2 diabetes, hypertension, cardiovascular disease. Reproductive: Infertility, miscarriage risk. Endometrial cancer risk: Due to unopposed estrogen. Non-alcoholic fatty liver disease (NAFLD).
107
How is PCOS treated?
Hirsutism: Shaving, waxing, OCPs, anti-androgens (cyproterone acetate, flutamide), spironolactone, finasteride. Menstrual regulation: OCPs, metformin (improves insulin resistance). Infertility treatment: Weight loss, ovulation induction (letrozole, clomiphene).
108
What is diabetes mellitus?
A chronic condition characterized by hyperglycemia due to insulin deficiency, resistance, or both. It is irreversible and leads to reduced life expectancy due to complications.
109
What is the characteristic lipid profile in diabetes?
Hypertriglyceridemia
Low HDL cholesterol
110
What are the types of diabetes?
Type 1 DM: Autoimmune β-cell destruction, leading to absolute insulin deficiency.
Type 2 DM: Insulin resistance with relative insulin deficiency.
LADA (Latent Autoimmune Diabetes in Adults): Slow-onset Type 1 DM in adults.
MODY (Maturity-Onset Diabetes of the Young): Monogenic form of diabetes.
Secondary Diabetes: Due to drugs, pancreatic disease, or endocrine disorders.
Gestational Diabetes: Diagnosed during pregnancy.
111
What are key features of Type 1 DM?
Autoimmune β-cell destruction with autoantibodies (GAD, IA-2, ZnT8).
Presents in childhood or adolescence with polyuria, polydipsia, and weight loss.
Associated with other autoimmune diseases (e.g., Hashimoto’s, Addison’s, celiac disease).
Requires lifelong insulin therapy.
112
What are key features of Type 2 DM?
Insulin resistance with β-cell dysfunction.
Strong genetic component (90% concordance in twins).
Associated with obesity, metabolic syndrome, hypertension, dyslipidemia.
25-50% of patients have vascular complications at diagnosis.
Progresses from impaired glucose tolerance (IGT) & FBG to diabetes.
β-cell mass reduced to 50% at diagnosis.
Amyloid deposition in pancreatic islets.
113
What are the clinical features of diabetes?
Classic triad: Polyuria, polydipsia, nocturia.
Weight loss (Type 1 > Type 2).
Blurred vision (lens swelling due to hyperosmolarity).
Genital thrush, recurrent infections (Candida, skin sepsis).
May present with diabetic complications (retinopathy, nephropathy).
114
What are other causes of diabetes?
Gestational diabetes
Drugs: Steroids, anti-HIV drugs, antipsychotics, thiazides.
Pancreatic disease: Pancreatitis, CF, hemochromatosis, cancer.
Endocrine disorders: Cushing’s, acromegaly, pheochromocytoma, hyperthyroidism.
Genetic syndromes: Down, Turner, glycogen storage diseases.
115
What is LADA (Latent Autoimmune Diabetes in Adults)?
A variant of Type 1 DM that occurs after age 30 with slow β-cell destruction.
Presents initially like Type 2 DM but progresses to insulin dependence within 6 months.
Positive for autoantibodies (GAD, islet cell antibodies).
Not associated with obesity or metabolic syndrome.
116
How is LADA diagnosed?
Non-obese adult with progressive insulin dependence.
Positive autoantibodies (GAD, islet cell antibodies).
Low C-peptide levels (reflecting low insulin production).
117
What is MODY (Maturity-Onset Diabetes of the Young)?
Rare monogenic diabetes that presents before age 25.
Autosomal dominant inheritance (most commonly HNF-1 gene mutation).
Not associated with obesity or metabolic syndrome.
Slowly progressive hyperglycemia, controlled with diet or oral medications.
118
How is MODY diagnosed?
Strong family history (affecting multiple generations).
Onset < 25 years old.
Not insulin-dependent at diagnosis.
Genetic testing confirms diagnosis (HNF-1 gene mutation most common).
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What are the diagnostic criteria for prediabetes?
IFG: Fasting glucose 5.6–6.9 mmol/L.
IGT: 2-hour OGTT glucose 7.8–11.0 mmol/L.
HbA1C: 5.7–6.4% (39–47 mmol/mol).
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What is the diagnostic criteria for diabetes?
Fasting glucose ≥7.0 mmol/L (twice if asymptomatic).
Random glucose ≥11.1 mmol/L + symptoms.
2-hour OGTT ≥11.1 mmol/L.
HbA1C ≥6.5%.
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What are the chronic complications of diabetes?
Microvascular: Retinopathy, nephropathy, neuropathy. (Glycemic control more effective w/ micro)
Macrovascular: Coronary artery disease (CAD), peripheral arterial disease (PAD), stroke.
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What are the cardiovascular complications in diabetes?
Leading cause of death in diabetics.
Atherosclerosis → MI, stroke, heart failure.
Most common lipid pattern: High triglycerides, low HDL.
LDL goal: <100 mg/dL → Use statins if higher.
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What are the types of diabetic retinopathy?
Background retinopathy: Microaneurysms, hemorrhages, hard exudates.
Pre-proliferative retinopathy: Cotton-wool spots, venous beading.
Proliferative retinopathy: Neovascularization, vitreous hemorrhage.
Maculopathy: Macular edema affecting vision.
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How often should diabetic patients be screened for retinopathy?
For type 1 diabetes: First screening 5 years after diagnosis, then annually.
For type 2 diabetes: At diagnosis, then annually.
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What are the types of diabetic neuropathy?
Peripheral: Numbness, paresthesia, pain, absent reflexes.
Mononeuropathy: Sudden foot drop, wrist drop, CN III, IV, VI palsies.
Autonomic: Orthostatic hypotension, gastroparesis, urinary retention, erectile dysfunction, constipation/diarrhea.
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What should be checked at each visit for diabetic patients?
Blood sugar monitoring and treatment.
Episodes of low blood sugar (if on insulin or sulfonylurea).
Adjust treatment targets if needed.
Address any problems or questions.
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What tests should be done yearly for diabetic patients?
HbA1c (average blood sugar).
Blood pressure and weight.
Blood lipids (cholesterol and triglycerides).
Kidney tests (urine for protein and blood for creatinine).
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What exams should be done yearly for diabetic patients?
Eye check for retina and vision.
Foot check for pulses and nerve issues.
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What else is reviewed yearly for diabetic patients?
Heart disease risks, eating habits, and self-care techniques.
Education on managing diabetes.
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What are the main oral hypoglycemic drugs?
Metformin: 1st-line
Sulfonylureas (glibenclamide, gliclazide)
Thiazolidinediones (pioglitazone)
incretins: GLP-1 analogues (exenatide, liraglutide) and GLIPTINS (sitagliptin, saxagliptin)
SGLT2 inhibitors (dapagliflozin, empagliflozin)
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What is the first step in treating type 2 diabetes?
Lifestyle changes: healthy diet, regular exercise, and weight management.
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What are medication regimes for T2DM if lifestyle changes are not enough?
Monotherapy Metformin. If that doesn't work add SGLT2 inhibitor or GLP-1 receptor agonist (heart disease or kidney issues).
If two medications don’t work: Triple therapy: Metformin + SGLT2 inhibitor + GLP-1 receptor agonist.
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What happens if triple therapy doesn’t work?
Start insulin therapy.
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When are sulfonylureas or thiazolidinediones used?
Only when cost is a concern due to their side effects.
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What are the types of insulin?
Rapid-acting: Lispro, Aspart (novorapid), glulisin (onset 3-15 min, peak 45-75 min).
Short-acting: Regular insulin (onset 30 min, peak 2-4 hrs).
Intermediate: NPH (peak 4-12 hrs, duration 12-18 hrs).
Long-acting: Glargine, Detemir, Degludec (no peak, >24 hrs).
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What are the complications of insulin therapy?
Hypoglycemia (most common)
Weight gain.
Lipohypertrophy.
Lipoatrophy.
Local allergic reactions.
Insulin resistance.
Rarely injection site abscesses.
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What is the definition of hypoglycemia?
Plasma glucose <3 mmol/L.
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What are the symptoms of hypoglycemia?
Autonomic: Sweating, anxiety, hunger, tremor, palpitations, dizziness.
Neuroglycopenic: Confusion, drowsiness, seizures, visual impairment, coma.
Personality changes, restlessness, incoherence.
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What are the common causes of hypoglycemia?
Diabetes treatment errors: Insulin or sulfonylurea use w/ missed meals, increased activity.
Exogenous drugs: Alcohol, aspirin poisoning, pentamidine, quinine.
Sulfonylurea abuse: Elevated C-peptide and proinsulin levels.
Surreptitious insulin use: Low C-peptide and proinsulin.
Medical conditions: Liver failure.
Addison’s disease.
Pituitary insufficiency.
Tumors: Insulinoma, immune hypoglycemia (Hodgkins disease), fibrosarcoma, hemangiopericytoma.
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What is Whipple's triad for diagnosing hypoglycemia?
Symptoms of hypoglycemia.
Low plasma glucose concentration.
Resolution of symptoms after glucose normalization.
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How is hypoglycemia diagnosed?
Confirm with finger-prick or lab glucose during an episode.
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What are the investigations for underlying causes of hypoglycemia?
C-peptide levels: elevated in endogenous, Low in exogenous insulin use.
Insulin to C-peptide ratio (>1.0 indicates exogenous insulin use).
Sulfonylurea testing (urine and blood)(Low glucose with high insulin and C-peptide).
72-hour fasting test for insulinoma.
Endocrine tests (pituitary & adrenal function).
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How is hypoglycemia treated in conscious patients?
Rapidly absorbed carbohydrate:
Toast, non-diet soda, or
GlucoGel orally (40% dextrose gel).
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How is hypoglycemia treated in unconscious patients?
IV dextrose: (50 mL of 20% dextrose) followed by saline flush.
IM glucagon (1 mg): Mobilizes hepatic glycogen.
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What should be done for patients with recurrent hypoglycemia after treatment?
Monitor blood glucose hourly (4-hourly when stable).
Consider a 10% dextrose infusion to prevent recurrence.
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What is diabetic ketoacidosis (DKA)?
Hyperglycemia (>11 mmol/L).
Ketosis (urine & serum ketones).
Metabolic acidosis (pH <7.3, HCO3 <18, anion gap >12).
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What are the causes of DKA?
Infection, insulin noncompliance, new-onset diabetes.
Severe illness (MI, stroke, pancreatitis).
Pregnancy, or no precipitating events.
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What is the treatment for DKA?
IV fluids (normal saline → add dextrose when glucose <14 mmol/L).
IV insulin (0.1 U/kg/hr).
Potassium replacement.
Sodium bicarbonate if pH < 7.
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What are the criteria for the resolution of diabetic ketoacidosis (DKA)?
Blood glucose <11 mmol/L.
At least two of the following:
Bicarbonate ≥15 mmol/L.
pH >7.3.
Anion gap ≤12.
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What are the key features of HHNS?
Affects mainly type 2 diabetics, especially older adults.
Extreme hyperglycemia (>33.3 mmol/L).
High plasma osmolality (>320 mOsm/kg).
No ketosis or acidosis.
Gradual onset, often triggered by illness or infection.
Severe dehydration, stupor, or coma due to hyperosmolarity.
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How is HHNS treated?
Fluids: Correct dehydration (normal saline initially).
Insulin: Lower glucose gradually.
Electrolytes: Monitor and replace potassium as needed.
Treat underlying cause (e.g., infection).
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What is the target glucose and osmolality reduction in HHNS treatment?
Blood glucose should fall by 4–6 mmol/L/hour.
Plasma osmolality should decrease by 3–8 mOsm/kg/hour.
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What is diabetes insipidus (DI)?
Deficiency of ADH (central) or renal resistance to ADH (nephrogenic).
Polyuria, polydipsia, hypernatremia.
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What are the main causes of diabetes insipidus?
Central DI (reduced ADH production): Brain injury/trauma/tumors.
Infections (TB, syphilis).
Infiltrative diseases (sarcoidosis).
Nephrogenic DI (kidney resistance to ADH): CKD (e.g., pyelonephritis, amyloidosis, sickle cell disease).
Hypercalcemia.
Hypokalemia.
Medications: Lithium/Demeclocycline.
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How is diabetes insipidus diagnosed?
Water deprivation test:
Urine osmolality high → primary polydipsia (psychogenic DI).
Urine osmolality remains low → Give desmopressin.
Response to desmopressin:
Central DI: Urine osmolality increases.
Nephrogenic DI: No change in urine osmolality.
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How is diabetes insipidus treated?
Central DI:
Desmopressin
Chlorpromide
Treat the underlying cause.
Nephrogenic DI:
Treat the underlying cause.
Na restriction.
Thiazide, amiloride.
NSAIDs: indomethacin.
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what are other clinical symptoms of pheochromocytoma ?
weakness, fa8gue, tremor, anxiety, weight loss , flushing, paresthesia, tachycardia, orthostatic hypotension, diaphoresis
• May have high WBCs, RBCs, glucose, lactic acidosis
