Notes on Endocrine Disorders

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Negaive feedback loops:

• Control level of hormone production.

• Stimulation tests evaluate hypofunction.

• Suppression tests evaluate hyperfunction.

Hypothalamus disorders: findings:

• Secondary hypopititarism.

• Central diabetes insipidus.

• Hyperprolactinemia.

• Precocious puberty.

• Visual disturbances.

• Mass effects.

• Growth defects.

• Kallmann's syndrome.

Pineal gland disorders: findings:

• Visual disturbances.

• Obstructive hydrocephalus.

Pituitary gland disorders:

Anterior pituitary: hypofunction:

Causes:

• Pituitary disease.

• Hypothalamic disorder.

• Nonfunctioning pituitary adenoma.

• Decreased: FSH, LH, GH, TSH, ACTH.

• Sheehan's postpartum necrosis.

Craniopharyngioma:

• Benign pituitary tumor in children.

Pituitary apoplexy:

• Hemorrhage/infarction of a pituitary adenoma.

Posterior pituitary hypofunction:

• Central diabetes insipidus (CDI) due to lack of ADH; treat with desmopressin.

• Nephrogenic diabetes insipidus (NDI) due to drugs, hypokalemia, nephrocalcinosis; treat with thiazides.

Findings:

• Thirst, polyuria.

• Lab findings: hypernatremia, hypotonic urine.

• Water deprivation test: increased plasma and urine osmolarity.

• Usual findings in CDI and NDI: increased plasma osmolarity and decreased urine osmolarity.

Findings after ADH injection:

• CDI: increased urine osmolarity.

• NDI: increased urine osmolarity.

Pituitary Hyperfunction Disorders:

Prolactinemia:

• Benign adenoma; most common.

• Findings in women: amenorrhea; galactorrhea.

• Findings in men: impotence.

• Decreased FSH, LH, GnRH.

• Treatment: dopamine analogues.

Growth hormone:

• Gigantism in children.

• Acromegaly in adults.

• Increased GH, IGF-1.

Syndrome of Inappropriate ADH (SIADH):

• Causes: small cell carcinoma of lung, CNS injury, drugs, pulmonary infections.

• Findings: mental status dysfunction, hyponatremia.

• Restrict water intake.

Thyroid gland disorders:

Function tests:

• Total serum T4:

• Represents bound (to TBG) and unbound serum T4.

• Increased TBG synthesis increases T4 and vice versa.

Serum TSH:

• Best indicator of thyroid function.

• Increased TSH: primary hypothyroidism.

• Decreased TSH: thyrotoxicosis (Grave's disease); hypopituitarism.

I-131 uptake:

• Indicates synthetic activity of thyroid.

• Increased I-131 uptake: increased T4 synthesis; also, hot nodule / goiter.

• Decreased I-131 uptake: decreased gland activity; also cold nodule / cancer.

Thyroglobulin:

• Thyroid marker.

Lingual Thyroid:

• Failed descent of thyroid; dysphagia, mass lesion; I-131 locates lesion.

Thyroiditis:

Acute:

• Bacterial infections.

• Findings: fever, tenderness, thyrotoxicosis followed by permanent hypothyroidism.

• Decreased I-131 uptake.

Subacute Granulomatous Thyroiditis:

• Viral infections.

• Women 40-50 years old.

• Findings: pain, pulmonary infection, thyrotoxicosis followed by permanent hypothyroidism.

• Decreased I-131 uptake.

Hashimoto's thyroiditis:

• Autoimmune thyroid destruction.

• HLA-Dr3 and Dr5.

• Enlarged.

Findings:

• Thyrotoxicosis followed by hypothyroidism.

Reidel's thyroiditis:

• Gland replaced by fibrous tissue.

Subacute Painless Lymphocytic Thyroiditis:

• Autoimmune disease that develops postpartum.

Findings:

• Thyrotoxicosis, enlargement.

Hypothyroidism:

Causes:

• Hashimoto's thyroiditis, cretinism.

Findings:

• Weight gain, fatigue, cold intolerance, constipation, hypertension, muscular myopathy.

Lab findings:

• Decreased T4, increased TSH; antimicrosomal and antithyroglobulin antibodies, hypercholesterolemia.

Treatment:

• Levothyroxine.

Excess thyroid hormone:

• Due to: thyrotoxicosis and hyperthyroidism.

Findings:

• Increased BMR.

Graves' disease:

• HLA-Dr3; IgG against TSH receptor.

• Hyperthyroidism and thyrotoxicosis.

Findings:

• Exophthalmos, pretibial myxedema.

Plummer's disease:

• Goiter.

Thyrotoxicosis: findings:

• Weight loss, fine hand tremor, heat intolerance, diarrhea, anxiety, lid stare, tachycardia, atrial fibrillation, hypertension, HF.

Lab findings:

• Increased T4, decreased TSH.

• Increased I-131 uptake in Graves' disease and goiter.

• Decreased I-131 uptake in thyroiditis and patients taking excess thyroid hormone.

• Hyperglycemia, hypocholesterolemia, hypercalcemia, lymphocytosis.

Treatment of Graves' disease:

• Beta-blockers; thionamides.

Nontoxic goiter:

• Enlargement from excess colloid.

• Deficiency of thyroid hormone.

• Hyperplasia/hypertrophy.

• Treatment: levothyroxine.

Types of goiters:

Endemic:

• Iodide deficiency.

Sporadic:

• Goitrogens (eg., cabbage), enzyme deficiency, puberty, pregnancy.

Thyroid tumors:

• Follicular adenoma: most common benign tumor.

• Papillary adenocarcinoma: radiation exposure; female dominant; Orphan-Annie nuclei; spreads to cervical nodes, lungs.

• Follicular carcinoma: most common female dominant thyroid cancer; spreads to lungs and bone.

• Medullary carcinoma: MEN IIa/IIb.

MEN IIa:

• Medullary carcinoma, hyperparathyroidism, pheochromocytoma.

MEN IIb/III:

• Medullary carcinoma, mucosal neuromas, pheochromocytoma.

Parafollicular C cell tumors:

• RET proto-oncogene.

• Ectopic production of ACTH.

Parathyroid gland disorders:

Hypoparathyroidism:

• Hypocalcemia.

• Causes: surgery, autoimmune, DiGeorge syndrome, hypomagnesemia.

• Findings: tetany, basal ganglia calcification, cataracts.

• Lab: hypocalcemia, hyperphosphatemia, decreased PTH.

Primary hyperparathyroidism (HPTH):

• Common cause of hypercalcemia.

• MEN I/IIa association.

Causes:

• Adenoma.

• Primary hyperplasia.

• Carcinoma.

Findings:

• Calcium stones, peptic ulcers, acute pancreatitis, constipation, osteitis fibrosa cystica (salt and pepper appearance of skul), hypertension.

Lab:

• Increased PTH, Ca; decreased Ph; normal anion gap metabolic acidosis.

Diagnosis:

• Technetium-99-m-sestamibi radionuclide scan.

Treatment:

• Surgically remove adenoma.

Parathyroid gland disorders: secondary hyperparathyroidism:

• Hyperplasia of all parathyroid glands.

• Decreased Ca; increased PTH.

Phosphorus disorders:

Hypophosphatemia:

Causes:

• Hypovitaminosis D, insulin Rx, primary HPTH, alkalosis, vitamin D-resistant rickets.

Findings:

• Muscle weakness, RBC hemolysis.

Hyperphosphatemia:

Causes:

• Renal failure, normal childhood, primary hypoparathyroidism.

Findings:

• Metastatic calcification, hypovitaminosis D.

Adrenal Gland Disorders:

Hypofunction:

Acute adrenocortical insufficiency:

• Causes: Waterhouse-Friderichsen syndrome (N. meningitides, DIC, adrenal hemorrhage).

Chronic Addison's disease:

• Autoimmune.

• Tuberculosis/histoplasmosis.

• Adrenogenital symdrome.

• Metastasis.

• Findings: weakness, hypotension, hyperpigmentation.

Lab:

• ACTH test shows no increase in cortisol or 17-OH.

• Metyrapone test: increased ACTH only.

• Increased plasma ACTH.

• Hyponatremia, hyperkalemia, metabolic acidosis.

• Fasting hypoglycemia.

• Eosinophilia, lymphocytosis, neutropenia.

Adrenal gland disorders:

Adrenogenital syndrome:

• AR disease.

• Increased ACTH, 17-KS, testosterone, DHT, fluctuating mineralocorticoid levels, 21-hydroxylase deficiency, 11-hydroxylase deficiency, 17-hydroxylse deficiency.

Hyperfunction:

Causes:

• Cushing syndrome.

Findings:

• Weight gain, muscle weakness, hypertension, hirsutism, purple abdominal stria, osteoporosis.

Lab:

• Increased cortisol in urine, cannot suppress low-dose dexamethasone (but only in pituitary Cushing syndrome), hyperglycemia, hypokalemic metabolic acidosis, Nelson's syndrome (enlargement of pituitary adenoma).

Hyperaldosteronism:

Primary:

• AKA Conn's syndrome.

• Findings: Hypertension, muscle weakness, tetany, metabolic acidosis.

• Labs: hypernatremia, hypokalemia, metabolic alkalosis, decreased plasma rennin.

Secondary:

• Compensatory reaction to decreased cardiac output.

• Increased plasma rennin.

• Activated rennin-angiotensin-aldosterone system.

Medulla hyperfunction:

• Increased catecholamines causes hypertension.

• Associated with: NF, MEN IIa/IIb, VHL disease.

Pheochromocytoma:

• Unilateral, benign adenoma.

• N-methyltransferase converts NOR to EPI.

• Characteristics: brown, hemorrhagic, necrotic.

• Findings: hypertension, palpitations, anxiety, sweats, headache, chest pain.

• Labs: increased urine VMA and metanephrine, hyperglycemia, neutrophilic leukocytosis.

Neuroblastoma:

Malignant tumor:

• Children younger than 5 years old.

• N-MYC oncogene amplification.

Small cell tumor:

• Homer-Wright rosettes.

• Palpable abdominal mass; hypertension.

• Spreads to skin and bones.

• Labs: increased VMA, metanephrines, HVA.

Islet cell tumors:

Diabetes mellitus:

Causes:

• Pancreatic, endocrine, or genetic disease; insulin-receptor deficiency; infections; impaired glucose tolerance; gestational diabetes mellitus.

• Younger patients.

• AD inheritance.

• HLA-DR3 and HLA-DR4 genetic associations.

Syndrome X:

• Insulin resistance.

• Hyperinsulinemia: increased VLDL, hypertension, coronary artery disease.

Pathology:

• Poor glycemic control: hyperglycemia.

• Nonenzymatic glycosylation: combination of glucose with proteins.

• Osmotic damage: damage to tissue, retina, vessels.

• Diabetic microangiopathy: decreased type IV collagen synthesis.

Findings:

• Hypoglycemia.

• Diabetic ketoacidosis.

• Hypertriglyceridemia.

• Muscle wasting.

• Labs: hyperglycemia, hyponaremia, hyperkalemia, increased anion gap metabolic acidosis, prerenal azotemia.

Gestational diabetes:

• Diabetes of pregnancy due to anti-insulin effect of human placental lactogen and increased placental size.

• Risk to newborns: macrosomia, RDS, neural tube defects, hypoglycemia.

Hypoglycemia:

Reactive type:

Causes:

• Insulin treatment for type 1 diabetes.

• IGT or type 2 diabetes.

• Idiopathic postprandial syndrome.

Findings:

• Sweating, trembling, anxiety.

Fasting type:

Causes:

• Alcohol, renal failure, malnutrition, liver disease, insulinoma, hypopituitarism, ketotic hypoglycemia in childhood.

Findings:

• Dizziness, confusion, headache, lack of concentration, motor disturbances, seizures, coma.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration
27. A Table of Bleeding Disorders
28. FAQ on Structure and Function of Red Blood Cells
29. FAQ on Components of Blood
30. Notes on Hemostatic Mechanisms
31. What is Fever?
32. What is Edema?
33. FAQ on Blood Pressure
34. FAQ on principles of fluid and flow dynamics of Blood
35. Causes of Thrombocytopenia
36. Squamous cell carcinoma of head and neck mucosa
37. Four tumors which never metastasize to the brain
38. What is caustic injury?
39. What causes Peripheral Edema?

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