Endocrine Flashcards
Growth hormone adenomas of the anterior pituitary produce ______ in children, and ________ in adults.
Secondary ________ is also often present, because growth hormone reduces glucose uptake by cells
Gigantism; acromegaly
Diabetes
Diagnosis of growth hormone adenoma may be based on elevated GH and _____, as well as lack of GH suppression by oral _______
IGF-1; glucose
Treatment options for growth hormone adenomas
Octreotide
GH receptor antagonists
Surgery
Pt presents with poor lactation and loss of pubic hair following delivery of baby in which birth was complicated by hemorrhage. Most likely dx?
Sheehan syndrome
What hormones are made in the posterior pituitary?
NONE
ADH and Oxytocin are made in the hypothalamus and STORED in the posterior pituitary
Clinical features of central diabetes insipidus include polyuria, polydipsia, _____natremia and _____ serum osmolality, with ______ urine osmolality and specific gravity
Hypernatremia; high; low
What is the water deprivation test?
Used to dx diabetes insipidus
Positive if water deprivation fails to increase urine osmolality
Classic psychiatric drug associated with drug-induced nephrogenic diabetes insipidus
Lithium
Clinical features of SIADH include _____natremia and ______ serum osmolality, as well as mental status change and seizures
Hyponatremia; low
List potential causes of SIADH
Ectopic production (e.g., small cell carcinoma of the lung)
CNS trauma
Pulmonary infection (even in COPD)
Drugs (e.g., cyclophosphamide)
Treatment options for SIADH
Free water restriction
Demeclocycline — blocks effect of ADH
Hyperthyroidism involves increased level of circulating thyroid hormone, which increases the basal metabolic rate as well as the sympathetic nervous system activity.
How does thyroid hormone increase the BMR and SNS activity?
Increases BMR by increasing synthesis of Na/K-ATPase
Increases SNS activity by activity at beta-1 adrenergic receptors
How do cholesterol and glucose levels tend to change with hyperthyroidism?
Hypocholesterolemia
Hyperglycemia
What causes Grave’s disease?
Autoantibody (IgG) that stimulates TSH receptor, leading to increased synthesis and release of thyroid hormone
Most common cause of hyperthyroidism
Graves disease
Classic finding on histology indicating Graves disease
Scalloping of the colloid (along with diffuse hyperplasia)
Treatment options for Graves disease
Beta-blockers
Thioamide (blocks thyroid peroxidase)
Radioiodine ablation
One of the feared complications of Graves disease is thyroid storm, characterized by elevated _______ and massive hormone excess (stress) leading to arrhythmia, hyperthermia, and vomiting with hypovolemic shock.
This is treated with _____, ______, and ______
Catecholamines
PTU; beta-blockers; steroids
A multinodular goiter is an enlarged thyroid gland with multiple nodules, often due to relative ______ deficiency. It is usually nontoxic (euthyroid), but rarely the regions may become TSH-independent (‘toxic goiter’)
Iodine
______ = hypothyroidism in neonates and infants associated with mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia
Cretinism
Potential causes of cretinism
Maternal hypothyroidism during early pregnancy
Thyroid agenesis
Dyshormonogenetic goiter (most common enzyme deficiency is thyroid peroxidase)
Iodine deficiency
_______ = term for hypothyroidism in older children or adults characterized by weight gain despite normal appetite, slowing of mental activity, muscle weakness, and cold intolerance with decreased sweating
Myxedema
[myxedema refers to the fact that tissue appears edematous with dough-like consistency, but this is not due to fluid — it deposition of glycosaminoglycans. Classic areas of myxedema in hypothyroid are larynx (leads to deepening of voice) and tongue (appears enlarged)]
How do cholesterol levels change in hypothyroid?
Hypercholesterolemia
Hashimoto thyroiditis = autoimmune destruction of the thyroid associated with HLA-_____. This initially may present as hyperthyroidism, but progresses to hypothyroidism with decreased T4 and increased TSH.
________ and ________ antibotides are often present, which are markers of thyroid damage
DR5
Antithyroglobulin; antimicrosomal
Most common cause of hypothyroidism where iodine levels are sufficient
Hashimoto thyroiditis
Histological findings in pts with hashimoto thyroiditis
Chronic inflammation with formation of germinal centers
Hurthle cells
What cancer are pts with hashimoto thyroiditis at increased risk for?
Marginal zone B cell lymphoma
Granulomatous thyroiditis that follows a viral infection; presents as a tender thyroid with transient hyperthyroidism
Subacute (deQuervain) granulomatous thyroiditis
T/F: subacute (dequervain) thyroiditis presents with transient hyperthyroidism, and later progresses to hypothyroidism
False — it does present with transient hyperthyroidism, but this is self-limited and does NOT progress to hypothyroidism
Chronic inflammation with extensive fibrosis of the thyroid; presents as hypothyroidism with ‘hard as wood’ nontender thyroid gland. Fibrosis may extend to local structures (e.g., airway)
Reidel fibrosing thyroiditis
Both Reidel fibrosing thyroiditis and anaplastic thyroid carcinoma may progress to invade local structures (e.g., airway) — what is the main differentiating factor between these entities on patient presentation?
Reidel fibrosing thyroiditis classically occurs in a young female
Anaplastic thyroid carcinoma is a disease of the elderly
On 131-Iodine radioactive uptake studies, Graves disease or nodular goiter will show ______ uptake
Increased
On 131-Iodine radioactive uptake studies, adenoma and carcinoma will show ______ uptake, which warrants a _______ biopsy
Decreased; FNA
What is the mechanism for biopsy of the thyroid?
Fine needle aspiration (FNA)
Follicular adenoma is a thyroid neoplasm that is a benign proliferation of follicles surrounded by a fibrous capsule. Are these usually functional?
No, usually nonfunctional
[but rarely may secrete thyroid hormone]
4 types of thyroid carcinoma
Papillary carcinoma
Medullary carcinoma
Follicular carcinoma
Anaplastic carcinoma
Most common type of thyroid carcinoma
Papillary carcinoma (80% of cases)
Papillary carcinoma is the most common type of thyroid carcinoma. What is the major risk factor for developing it?
Exposure to ionizing radiation in childhood
Histologic features of papillary carcinoma of thyroid
Orphan Annie Eye Nuclei
Nuclear grooves
Psammoma bodies
Papillary carcinoma of the thyroid often spreads to the ______ nodes; it has a _______ prognosis
Cervical; excellent
Follicular carcinoma of the thyroid is a malignant proliferation of follicles surrounded by a fibrous capsule with INVASION through the capsule.
T/F: the gold-standard for differentiating follicular carcinoma and follicular adenoma is FNA biopsy
False — FNA would not allow you to assess for invasion beyond the capsule, result would be the same in either case just showing follicular cells
In order to assess/differentiate, would need to see gross specimen or look for microscopic signs of invasion on histology of the capsule itself
Follicular carcinoma of the thyroid is capable of metastasis, which generally occurs via _________ spread
Hematogenous
[note difference from papillary, which is lymphatic spread]
Medullary carcinoma of the thyroid is a malignant proliferation of ___________ cells, resulting in high levels of _______ produced by the tumor which may lead to lab finding of _________
Parafollicular C cells; calcitonin; hypocalcemia
With MTC, calcitonin often deposits within the tumor as _____
Amyloid
[characteristic histology description is malignant cells in an amyloid stroma]
Familial cases of medullary thyroid carcinoma are often due to ______ and _______ syndromes.
These are associated with mutations in the _____ oncogene, detection of which warrants prophylactic thyroidectomy
MEN2A; MEN2B
RET
Undifferentiated malignant tumor of the thyroid, usually seen in the elderly; often invades local structures leading to dysphagia or respiratory compromise and carries a poor prognosis
Anaplastic carcinoma
The key cell of the parathyroid gland is the _____ cell which regulates free (ionized) calcium via PTH secretion
Chief
3 major actions of PTH
Increases bone osteoclast activity (via osteoblast activation)
Increases small bowel absorption of calcium and phosphate (via Vitamin D activation)
Increases renal calcium reabsorption phosphate excretion
Primary hyperparathyroidism is excess PTH due to disorder of the gland itself. What is the most common cause?
Parathyroid adenoma (>80% of cases)
[other causes: sporadic hyperplasia, parathyroid carcinoma]
Parathyroid adenoma is a benign neoplasm, usually involving one gland, and most often resulting in asymptomatic hypercalcemia. If symptoms are present, what are they likely to be?
Nephrolithiasis (calcium oxalate)
Nephrocalcinosis (deposition in tubules —> renal insufficiency with polyuria)
CNS disturbance
Constipation, PUD, acute pancreatitis (calcium activates enzymes w/i pancreas)
Osteitis fibrosa cystica
[all consequences of increased PTH and hypercalcemia]
Lab findings in hyperparathyroidism including serum calcium, serum phosphate, urinary cAMP, and serum alkaline phosphatase
Increased serum calcium
Decreased serum phosphate
Increased urinary cAMP (PTH receptor is a Gs GPCR; activation results in increased cAMP)
Increased serum alkaline phosphatase
Secondary hyperparathyroidism is an excess production of PTH due to disease process extrinsic to parathyroid gland. What is the most common cause?
Chronic renal failure
[Renal insufficiency leads to decreased phosphate excretion. The increased serum phosphate binds free calcium, thus decreasing free serum calcium. This stimulates all four parathyroid glands leading to PTH release.]
Lab findings in secondary hyperparathyroidism including serum calcium, serum phosphate, and alkaline phosphatase
Decreased serum calcium
Increased serum phosphate
Increased alkaline phosphatase
[calcium is low because remember this process is driven by the fact that phosphate is high, which binds free calcium in the blood]
Hypoparathyroidism is defined as low PTH; causes include autoimmune damage, surgical excision, and ______ syndrome
DiGeorge
[failure to develop 3rd and 4th pharyngeal pouch]
Clinical presentation of hypoparathyroidism including labs (PTH, calcium)
Numbness and tingling (typically perioral)
Muscle spasms (tetany) — Trousseau or Chvostek’s sign
Decreased PTH and decreased serum calcium
_________ is due to end-organ resistance to PTH, often due to defect in Gs stimulatory protein.
The _______ ________ inherited form is associated with a short stature and short 4th and 5th digits
Pseudohypoparathyroidism
Autosomal dominant
Pseudohypoparathyroidism is due to end-organ resistance to PTH. Labs will show what changes in calcium and PTH levels?
Hypocalcemia
Increased PTH levels
The endocrine pancreas is composed of cells termed islets of langerhans. A single islet consists of multiple cell types, each producing one type of hormone. Insulin is secreted by ______ cells, which lie at the ______ of islets.
Glucagon is secreted by ______ cells
Beta; center
Alpha
T1D is caused by autoimmune destruction of beta cells by T lymphocytes, which is a type ____ HSR. This leads to inflammation of the islets.
T1D is associated with HLA-____ and _____. Autoantibodies against _____ are often present
Type IV HSR
DR3; DR4; insulin
DKA is a complication of T1D, and manifests due to excessive serum ketoacids. This often arises with stress (e.g., infection) in which _______ increases secretion of _______, exacerbating lipolysis (along with gluconeogenesis and glycogenolysis). The increased lipolysis leads to increased FFAs, which go to the liver where they are converted to ketone bodies.
Epinephrine; glucagon
DKA may present clinically with Kussmaul respirations, dehydration, nausea, vomiting, mental status change, and fruity smelling breath. What will labs show regarding glucose levels, blood gases, and potassium?
Hyperglycemia (>300 mg/dL)
Anion gap metabolic acidosis
Hyperkalemia
[note that while labs show hyperkalemia, this is an effect of cellular K+ loss, which will eventually be peed out, so on correction of DKA watch for signs of hypokalemia and replace K+ as needed]
Treatment for DKA
Fluids
Insulin
Replacement of electrolytes (e.g., potassium)
What is the mechanism of insulin-resistance in obese pts with T2D?
Obesity leads to decreased numbers of insulin receptors
In T2D, insulin levels are increased early in disease. Insulin deficiency develops later due to beta cell exhaustion. Histology reveals _____ deposition in islets
Amyloid
Laboratory diagnostic criteria for T2D (random glucose, fasting glucose, glucose tolerance test)
Random glucose > 200 mg/dL
Fasting glucose >126 mg/dL
Glucose tolerance test > 200 mg/dL two hours after glucose load
While the primary feared complication of T1D is DKA, the feared acute complication in T2D is _____________
[what are the clinical features?]
Hyperosmolar non-ketotic coma
Presents with high glucose levels (>500 mg/dL), leading to life-threatening diuresis, hypotension, and coma. Ketones are characteristically absent
2 major mechanisms by which complications of T2D arise
Non-enyzmatic glycosylation
Osmotic damage
One mechanism of complications in T2D is nonenzymatic glycosylation (NEG) of vascular basement membranes.
NEG of large- and medium-sized vessels leads to __________, which is the mechanism of CV disease in diabetes.
NEG of small vessels leads to _______ _________, which is the mechanism of diabetic nephropathy.
NEG of hemoglobin leads to ______.
Atherosclerosis
Hyaline arteriosclerosis
HbA1c
Another mechanism of complications in T2D is osmotic damage. This occurs when sugar enters certain cells and is converted to sorbitol by aldose reductase. What are the 3 primary tissues affected by osmotic damage in T2D?
Schwann cells — leads to peripheral neuropathy
Pericytes of retinal blood vessels — leads to retinopathy, hemorrhage, blindness
Lens — leads to cataracts
Pancreatic endocrine tumors are tumors of islet cells and are often a component of MEN1 (along with parathyroid hyperplasia and pituitary adenoma).
List the 5 different types of pancreatic endocrine tumors
Insulinoma
Gastrinoma
Somatostatinoma
Glucagonoma
VIPoma
Pancreatic endocrine tumor characterized by episodic hypoglycemia with mental status changes relieved by glucose
Insulinoma
Lab results (glucose, insulin, c-peptide) associated with insulinoma
Decreased glucose
Increased insulin
Increased c-peptide
Pancreatic endocrine tumor characterized by treatment-resistant peptic ulcers; may be multiple and can extend to jejunum
Gastrinoma
[treatment resistant peptic ulcers = zollinger ellison syndrome]
Pancreatic endocrine tumor characterized by achlorhydria, cholelithiasis, and steatorrhea
Somatostatinoma
[achlorhydria is due to inhibition of gastrin; cholelithiasis and steatorrhea due to inhibition of CCK]
Pancreatic endocrine tumor characterized by watery diarrhea, hypokalemia, and achlorhydria
VIPoma
3 layers of adrenal cortex and their products
Glomerulosa — mineralocorticoids (aldosterone)
Fasciculata — glucocorticoids (cortisol)
Reticularis — sex steroids
What are 3 ways cortisol causes immune suppression?
Inhibition of phospholipase A2 — can’t generate arachidonic acid metabolites
Inhibition of IL-2 — immune cell growth factor
Inhibition of histamine release from mast cells — essential for vasodilation and increased vascular permeability in immune response
Diagnostic test for Cushing syndrome
Increased 24-hour urine cortisol level
4 major causes of Cushing syndrome
Exogenous corticosteroids (most common cause)
Primary adrenal adenoma, hyperplasia, or carcinoma
ACTH-secreting pituitary adenoma
Paraneoplastic ACTH secretion (classically small cell carcinoma of the lung)
In differentiating the causes of cushing syndrome, you can look at the size of the adrenals. In exogenous corticosteroid use, both adrenals become atrophied. In primary adrenal hyperplasia/adenoma/carcinoma, the contralateral adrenal will be atrophied.
However, in both ACTH-secreting pituitary adenoma AND paraneoplastic ACTH secretion, both adrenals will be hyperplastic — so you can tell them apart based on this. So how do you differentiate between ACTH-secreting pituitary adenoma and paraneoplastic ACTH secretion as the underlying cause of cushing syndrome?
High-dose dexamethasone suppression test
This will suppress ACTH production by a pituitary adenoma, but will FAIL to suppress ectopic ACTH production by a small cell lung carcinoma
Hyperaldosteronism results in HTN as well as what changes in sodium, potassium, and blood gases?
Hypernatremia
Hypokalemia
Metabolic alkalosis
Primary hyperaldosteronism is most commonly due to ______ _____. Sporadic hyperplasia and carcinoma are less common causes. This condition is characterized by _____ aldosterone and _____ renin
Adrenal adenoma; high; low
Secondary hyperaldosteronism involves activation of the RAAS (e.g., renovascular HTN), and is characterized by _____ aldosterone and _____ renin
High; high
Congenital adrenal hyperplasia is characterized by excess sex steroids with hyperplasia of both adrenal glands. A _______ deficiency is the most common cause, in which steroidogenesis is shunted towards sex steroid production
21-hydroxylase
In 21-hydroxylase deficiency, there is a deficiency of ______ which leads to increased _____, which results in bilateral adrenal hyperplasia
Cortisol; ACTH
Clinical features of 21-hydroxylase deficiency
Salt wasting with hyponatremia, hyperkalemia, and hypovolemia
Life-threatening hypotension
Clitoral enlargement (females) or precocious puberty (males)
Adrenal insufficiency = lack of adrenal hormones. This may arise acutely with ___________ syndrome resulting in bilateral adrenal hemorrhage, classically in the setting of Neisseria infection in which child develops DIC and massive hypotension due to lack of cortisol
Waterhouse-Friderichsen syndrome
Chronic adrenal insufficiency may arise due to progressive destruction of adrenal glands, autoimmune destruction, TB, or metastatic carcinoma. The classic metastatic carcinoma that goes to the adrenal glands is ______ cancer
Lung
Clinical features of adrenal insufficiency
Hypotension
Hyponatremia, hypovolemia, hyperkalemia
Weakness
Hyperpigmentation
Vomiting and diarrhea
The adrenal medulla is composed of _____ _____-derived _______ cells. These are the main source of catecholamines (epinephrine and NE)
Neural crest; chromaffin
Brown tumor composed of chromaffin cells causing classic clinical manifestations of episodic HTN, headaches, palpitations, tachycardia, and sweating
Pheochromocytoma
Diagnosis of pheochromocytoma
Increased serum metanephrines
Increased 24-hour urine metanephrines and VMA
Treatment for pheochromocytoma is surgical excision. _______ must be given prior to surgery to prevent effects of excessive catecholamine release
Phenoxybenzamine
Rule of 10s for pheochromocytoma
10% bilateral
10% familial
10% malignant
10% located outside adrenal medulla
10% of pheochromocytomas are located outside the adrenal medulla. What is one classic location?
Bladder wall
3 syndrome associations with pheochromocytoma
MEN2A and 2B
VHL disease
NF type 1
