Endocrinology- Pathology (2) Flashcards
Diagnosing parathyroid disease
Pag. 339
Hypoparathyroidism
- Etiology
- Findings
Due to accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome.
Findings: tetany, hypocalcemia, hyperphosphatemia
Chvostek sign—tapping of facial nerve (tap the Cheek) contraction of facial muscles.
Trousseau sign—occlusion of brachial artery with BP cuff (cuff the Triceps) carpal spasm.
Pseudohypoparathyroidism type 1A
unresponsiveness of kidney to PTH hypocalcemia
despite high PTH levels.
Constellation of physical findings known as Albright hereditary osteodystrophy: shortened 4th/5th digits, short stature, obesity, developmental delay. Autosomal
dominant.
Due to defective Gs protein α-subunit causing end-organ resistance to PTH. Defect must be inherited from mother due to imprinting
Pseudopseudohypoparathyroidism
physical exam features of Albright hereditary osteodystrophy but without end-organ PTH resistance (PTH level normal). Occurs when defective Gs protein α-subunit is inherited from father.
Primary hyperparathyroidism
- Etiology
- Findings
Usually due to parathyroid adenoma or hyperplasia.
Hypercalcemia, hypercalciuria (renal stones), polyuria (thrones), hypophosphatemia, high PTH, high ALP, high cAMP in urine.
May present with weakness and constipation (groans), abdominal/flank pain, neuropsychiatric disturbances (“psychiatric overtones”).
“Stones, thrones, bones, groans, and psychiatric overtones.”
Secondary hyperparathyroidism
2° hyperplasia due to low Ca2+ absorption and/or high PO4, most often in chronic renal disease.
Hypocalcemia, hyperphosphatemia in chronic renal failure (vs hypophosphatemia with most other causes), high ALP, high PTH.
Tertiary hyperparathyroidism
Refractory (autonomous) hyperparathyroidism
resulting from chronic renal disease. High PTH,
HighCa2+.
Osteitis fibrosa cystica
cystic bone spaces filled with brown fibrous tissue (“brown tumor” consisting of osteoclasts and deposited
hemosiderin from hemorrhages; causes bone pain).
Due to High PTH, classically associated with 1° (but also seen with 2°) hyperparathyroidism.
Renal osteodystrophy
renal disease 2° andb3° hyperparathyroidism bone lesions.
Familial hypocalciuric hypercalcemia
Defective G-coupled Ca2+-sensing receptors in multiple tissues (eg, parathyroids, kidneys).
Higher than normal Ca2+ levels required to suppress PTH. Excessive renal Ca2+ reuptake mild hypercalcemia and hypocalciuria with normal to high PTH levels.
Nelson syndrome
Enlargement of existing ACTH-secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease.
Presents with hyperpigmentation, headaches and bitemporal hemianopia.
Treatment: pituitary irradiation or surgical resection.
Acromegaly
- Etiology
- Findings
Excess GH in adults. Typically caused by pituitary adenoma.
Large tongue with deep furrows, deep voice, large hands and feet, coarsening of facial features with aging, frontal bossing, diaphoresis (excessive sweating), impaired glucose tolerance (insulin resistance), hypertension. Risk of colorectal polyps and cancer.
Acromegaly
- Diagnosis
High serum IGF-1; failure to suppress serum GH following oral glucose tolerance test; pituitary mass seen on brain MRI.
Acromegaly
- Treatment
Pituitary adenoma resection. If not cured, treat with octreotide (somatostatin analog) or pegvisomant (growth hormone receptor antagonist), dopamine agonists (eg, cabergoline)
Laron syndrome
dwarfism
Defective growth hormone receptors decrease linear growth. High GH, Low IGF-1.
Clinical features: short height, small head circumference, characteristic facies with saddle nose and prominent forehead, delayed skeletal maturation, small genitalia.
Diabetes insipidus
- Clinical features
- Etiology
- General findings
Characterized by intense thirst and polyuria with inability to concentrate urine due to lack of ADH (central) or failure of response to circulating ADH (nephrogenic).
Urine specific gravity < 1.006
Serum osmolality > 290 mOsm/kg
Hyperosmotic volume contraction
Central DI
- Etiology
- Findings
- Water deprivation test
- Treatment
Pituitary tumor, autoimmune, trauma, surgery, ischemic encephalopathy, idiopathic
Low ADH
> 50% increase in urine osmolality only after administration of ADH analog.
Desmopressin + Hydration
Nephrogenic DI
- Etiology
- Findings
Hereditary (ADH receptor mutation), 2° to hypercalcemia, hypokalemia, lithium, demeclocycline (ADH antagonist).
Normal or High ADH levels
Nephrogenic DI
- Water deprivation test
- Treatment
Minimal change in urine osmolality, even after administration of ADH analog.
HCTZ, indomethacin, amiloride + Hydration, dietary salt restriction, avoidance of offending agent
Water deprivation test
No water intake for 2–3 hr followed by hourly measurements of urine volume and osmolality and plasma Na+ concentration and osmolality.
ADH analog (desmopressin) is administered if serum osmolality > 295–300 mOsm/kg, plasma Na+ ≥ 145 mEq/L, or urine osmolality does not rise despite a rising plasma osmolality
Syndrome of inappropriate antidiuretic hormone secretion
- Characterized by
Excessive free water retention
Euvolemic hyponatremia with continued urinary Na+ excretion.
Urine osmolality > serum osmolality
Why SIADH an eouvolemic hyponatremia?
Body responds to water retention with decrease aldosterone and high ANP and BNP increase urinary Na+ secretion normalization of extracellular fluid volume euvolemic hyponatremia.
SIADH causes include:
Ectopic ADH (eg, small cell lung cancer)
CNS disorders/head trauma
Pulmonary disease
Drugs (eg, cyclophosphamide
SIADH treatment
Treatment: fluid restriction (first line), salt tablets, IV hypertonic saline, diuretics, conivaptan, tolvaptan, demeclocycline.
*Increased urine osmolality during water deprivation test indicates psychogenic polydipsia.
Hypopituitarism
- etiology
Nonsecreting pituitary adenoma, craniopharyngioma
Sheehan syndrome
Empty Sella syndrome
Pituitary apoplexy
Brain injury
Radiation
Empty sella syndrome
Pituitary apoplexy
atrophy or compression of pituitary (which lies in the sella turcica), often idiopathic, common in obese women; associated with idiopathic intracranial hypertension.
sudden hemorrhage of pituitary gland, often in the presence of an existing pituitary adenoma. Usually presents with sudden onset severe headache, visual impairment, and features of hypopituitarism.
Hyperosmolar hyperglycemic state
- Diagnosis
Labs: hyperglycemia (often > 600 mg/dL), high serum osmolality (> 320 mOsm/kg), no acidosis (pH > 7.35, ketone production inhibited by presence of insulin).
Glucagonoma
- clinical features
- Treatment
Presents with dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight, depression.
Treatment: octreotide, surgery
Insulinoma
- Clinical Features
- Labs
- Treatment
May see Whipple triad: low blood glucose, symptoms of hypoglycemia (eg, lethargy, syncope, diplopia), and resolution of symptoms after normalization of glucose levels.
Symptomatic patients have low blood glucose and
high C-peptide levels (vs exogenous insulin use).
∼ 10% of cases associated with MEN 1 syndrome.
Treatment: surgical resection.
Somatostatinoma
- Clinical features
- Treatent
Decrease secretion of secretin, cholecystokinin, glucagon, insulin, gastrin, gastric inhibitory peptide (GIP).
May present with diabetes/glucose intolerance, steatorrhea, gallstones, achlorhydria.
Treatment: surgical resection; somatostatin analogs (eg, octreotide) for symptom control.
Carcinoid syndrome
- Etiology
Rare syndrome caused by carcinoid tumors (neuroendocrine cells; note prominent rosettes), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT). Not seen if tumor is
limited to GI tract (5-HT undergoes first-pass metabolism in liver).
Carcinoid syndrome
- Clinical features
- Labs
- Treatment
Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right-sided valvular heart disease (tricuspid regurgitation, pulmonic stenosis).
5-hydroxyindoleacetic acid (5‑HIAA) in urine, niacin deficiency (pellagra). Associated with neuroendocrine tumor markers chromogranin A and synaptophysin.
Treatment: surgical resection, somatostatin analog (eg, octreotide).
Carcinoid syndrome
- Rule of 1/3s:
1/3 metastasize
1/3 present with 2nd malignancy
1/3 are multiple
Most common malignancy in the small intestine
Zollinger-Ellison syndrome
- Clinical features
- Diagnosis
Acid hypersecretion causes recurrent ulcers in duodenum and jejunum. Presents with abdominal pain, diarrhea (malabsorption).
Positive secretin stimulation test: gastrin levels remain
elevated after administration of secretin, which normally inhibits gastrin release.
May be associated with MEN 1.
Multiple endocrine neoplasias
“All MEN are dominant” (autosomal dominant)
MEN 1
3 Ps:
Pituitary tumors (prolactin or GH)
Pancreatic endocrine tumors
Parathyroid adenomas
Associated with mutation of MEN1 (menin, a tumor suppressor, chromosome 11), angiofibromas, collagenomas, meningiomas
MEN 2A
2 Ps:
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma (secretes catecholamines)
Associated with mutation in RET (codes for receptor tyrosine kinase) in cells of neural crest origin.
MEN 2B
1 P:
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal neuromas (oral/intestinal ganglioneuromatosis)
Associated with marfanoid habitus; mutation in RET gene
