Chapter 15: Endocrine Flashcards
Prolactinoma, GH cell adenoma, ACTH cell adenomas are all examples of what?
A pituitary adenoma - Benign tumor of the anterior pituitary
What Sx would a patient with a non-functional pituitary adenoma present with (3)?
- BITEMPORAL HEMIANOPSIA - compression of the optic chiasm
- Hypopituitarism: due to compression of normal pituitary tissue
- HA
What is the most common type of pituitary adenoma?
Prolactinoma
What are the presenting symptoms of a Prolactinoma?
Females: galactorrhea, amenorrhea
Males: decreased libido, headache
What is the treatment for a prolactinoma?
Dopamine agonists (Bromocriptine or cabergoline): - suppresses prolactin production (tumor shrinks) or surgery for larger lesion
How will a Growth hormone cell adenoma presentation differ in children vs adults?
Children: Gigantism - increased linear bone growth (epiphysies are not fused)
Adults: Acromegaly - enlarged bones of hands, fee, jaw; growth of visceral organs leading to dysfunction (Cardiac failure); enlarged tongue
-Secondary diabetes mellitus is often present
How is a GH cell adenoma diagnosed?
Elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose
What is the treatment of a CH cell adenoma?
Octreotide (somatostatin analog that suppressed GH release
GH receptor antagonist
Surgery
What will be the major complication associated with ACTH cella denomas?
Cushing sydnrome
How much of the pituitary parenchyma must be lost before symptoms will arise from hypopituitarism?
75%
Pituitary adenomas in adults or craniopharyngiomas in children will cause what pituitary issue due to mass effect or pituitary apoplexy?
Hypopituitarism
What is Sheehan syndrome?
Pregnancy-related infarction of the pituitary gland.
- Gland doubles in size during pregnancy, but blood supply does NOT increase significantly; blood loss during parturition precipitates infarction.
How will a mother with Sheenhan syndrome present?
Poor lactation, loss of pubic hair [secondary to decreased LH], and fatigue
-Will have hypopituitarism
What is Empty sella syndrome?
Congenital defect of the sella
- herniation of the arachnoid and CSF into the sella compresses and destroys the pituitary gland
- Pituitary gland is “absent” (empty sella) on imagine
- Is a cause of hypopituitarism
What is Central Diabetes Insipidus?
ADH deficiency
-Due to hypothalamic or posterior pituitary pathology
A patient presents with polyuria, polydipsia, hypernatremia, high serum osmolality, and low urine osmolality and specific gravity. He is is found to have an issue with the posterior pituitary gland. What does he have?
Central diabetes insipidus
How do you diagnose Central Diabetes Insipidus?
Water deprivatoin test FAILS to increase urine osmolality
How do you treat Central Diabetes insipidus?
Desmopressin (ADH analog)
What is nephrogenic diabetes insipidus?
Impaired renal response to ADH
- Due to inherited mutations or drugs [lithium, demeclocycline]
- No response to desmopressin
What is Syndrom of inappropriate ADH (SIADH) Secretion?
Excess ADH secretion
What causes SIADH?
Most often due to ectopic ADH production [small cell carcinoma of the lung]
-other causes: CNS trauma, pulmonary infection, and drugs [cyclophosphamide]
A patient presents with hyponatremia and low serum osmolality. The patient also has mental status changes and seizures. The patient is found to have excessive ADH secretion and a problem with the posterior pituitary. What do they have?
SIADH secretion
What is the treatment for SIADH secretion
Free water restriction or demeclocycline - blocks effect on ADH
What is a thyroglossal duct cyst, and where does it come from?
- Cystic dilation of thyroglossal duct remnant
- a persistent thyroglossal duct that did not involute - which then underwent cystic dilation.
- Presents as an anterior neck mass
*How does hyperthyroidism increase basal metabolic rate?
Due to increased synthesis of Na/K ATPase
*How does Hyperthyroidism increase sympathetic nervous system activity?
Due to increased expression of B1-adrenergic receptors
What are the 2 symptoms most characteristic of Hyperthyroidism?
Hypocholesterolemia
Hyperglycemia [due to gluconeogenesis and glycogenolysis]
What is Graves disease?
- Autoantibody [IgG] that stimulates TSH receptor (type II hypersensitivity)
- Leads to increased synthesis and release of thyroid hormone
- A type of hyperthyroidism
A patient present with hyperthyroidism, Diffuse goiter, exophthalmos and pretibial myxedema. Histology of the thyroid shows irregular follices with SCALLOPED COLLOID and chronic inflammation. What do they have?
Graves!
What is the most common cause of hyperthyroidism?
Graves Disease
- Classically occurs in women of childbearing age (20-40 years old)
Laboratory tests come back with an increased total and free T4; Decreased TSH; Hypocholesterolemia, and an increased serum glucose. Histological examination of the thyroid reveals irregular follices with scalloped colloid. What does the patient have?
Graves!
How do you treat Graves Disease?
Beta blockers
Thioamide - Blocks peroxidase
Radioiodine ablation
What is THYROID STORM
- is a potentially fatal complication
- Due to elevated catecholamines and massive hormone excess, usually in response to stress [surgery, childbirth]
- Presents as arrhythmia, hyperthermia, and vomiting with hypovolemic shock
What is the treatment for thyroid storm?
Propylthiouracil (PTU), Beta blcoers, and steroids
-*PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 to T3
What is a multinodular goiter
- enlarged thyroid gland with multiple nodules
- Due to relative iodine deficiency
- Usually nontoxic - euthyroid
- Rarely, regions becomes TSH-independent leading to T4 release and hyperthyroidism (“Toxic goiter”)
What is Cretinism?
-Hypothyroidism in neonates and infants
What characterizes cretinism?
-Mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, umbilical hernia.
What are the causes of Cretinism?
- Maternal hypothyroidism during early pregannce
- Thyroid agenesis
- Dyshormonogenetic goiter
- Iodine deficiency
What causes the dyshormonogenetic goiter seen in Cretinism
Is due to a congenital defect in thyroid hormone production;
-Most commonly involves THYROID PEROXIDASE
What is myxedema?
-Hypothroidism in older children or adults
What is the most causes of Myxedema?
- Iodien deficiency
- Hashimoto thyroiditis
- Other: drugs [lithium], surgical removal; radioablation of the thyroid
What are the most common symptoms of Myxedema?
- Based on decreased basal metabolic rate and decreased sympathetic nervous system activity
- Myxedema: accumulation of glycosaminoglycans in the skin and soft tissue; results in a deepening of voice and large tongue
- Hypercholesterolemia;
- Others: Weight gain despite normal appetite, slowing of mental activity, muscle weakness, cold intolerance with decreased sweating, bradycardia with decreased cardiac output, leading to shortness of breath and fatigue, oligomenorrhea, constipation
What is Hashimoto Thyroiditis?
- Autoimmune destruction of the thyroid gland; associated with HLA-DR5
- Most common cause of hypothyroidism in regions were iodidne levels are adequate
A patient presented iniitally with hyperthyroidism (due to follicular damage). This then pregressed to hypothyroidism, with Decreased T4 and increased TSH.
Antithyroglobulin and antimicrosmal antibodies are present. What do they have?
Hashimoto Thyroiditis
A histology slide shows Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles). What do they have?
Hasimoto Thyroiditis
A patient presents with Hasimoto Thyroiditis. Which disease are they at risk for and how does it present?
- B-cell (marginal zone) lymphoma
- Presents as an enlarging thyroid gland late in disease course
A patient presents with a TENDER THYROID with transient hyperthyroidism a week after getting over a nasty viral infection. He has some time of self-limiting Granulomatous thyroiditis. What do they most likely have and what will it progress to?
- Subacute Granulomatous (De Quervain) Thyroiditis
- This is self-limiting - this does NOT progress to hypothyroidism
Patient presents with hypothyroidism with a “HARD AS WOOD”, NON-tender thyroid gland. Biopsy shows chronic inflammation with extensive fibrosis of the thyroid. Fibrosis extends (sometiems) to local structs, but there are no malignant cells present. What is the Dx?
Reidel Fibrosing Thyroiditis
How will thyroid neoplasms present?
-Usually as a distinct, solitary nodule that is more likely to be benign than malignant.
How can we differentiate and characterize nodules:
- BIOPSY IS PERFORMED BY FINE NEEDLE ASPIRATION.
- I-131 radioactive uptake studies are useful to further characterize nodules.
- Increased uptake (‘hot’ nodule) is seen in Graves disease or nodluar goiter.
- Decreased uptake (‘cold’ nodule) is seen in adenoma and carcinoma. OFTEN WARRNTS BIOPSY
- Increased uptake (‘hot’ nodule) is seen in Graves disease or nodluar goiter.
What are the 5 types of Throid neoplasias?
Follicular adenoma Papillary carcinoma Follicular carcinoma Medullary carcinoma Anaplastic carcinoma
Histo slide reveals a Benign proliferation of follicles surrounded by a FIBROUS CAPSULE
which is nonfunctional. (some, rarely may secrete thyroid hormone). What do they have?
Follicular adenoma
What is the most common type of thyroid carcinoma (80%)?
Papillary carcinoma
A patient was exposed to ionizing radiation in childhood - which type of carcinoma is he at risk for now?
Papillary Carcinoma
Histology reveales papillae lined by cells with clear “orphan Annie eye” nuclei and nuclear grooves. (The papillae are often assoicated with psammoma bodies). This was found to spread to cervical (neck) lymph nodes but still has an excellent prognosis. What do they have?
Papillary Carcinoma
How would you differentiate between follicular carcinoma and follicular adenoma?
Follicular carcinoma has invasion through teh fibrous capsule with a malignant proliferation of follicles.
This distinction can NOT be made with FNA
Whats different about follicular carcinoma’s when compared to a generic carcinoma?
Metastasis generally occur hematogenously - NOT via the lymph
What cell type is the malignant proliferation in medullary carcinoma?
Parafollicular C cells
What does a biopsy o Medullary carcinoma look like?
Reveals sheets of malignant cells in an amyloid stroma
Famililar cases of Medullary Carcinoma are often due to what?
Multiple Endocrine Neoplasia (MEN) 2A and 2B which are associated with mutation in the RET oncogene.
-Men 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral muscosa (2B)
If a patient has detection of a RET mutation - what should happen?
Warrants prophylactic thyroidectomy
What age group do you normally see Anaplastic carcinoma in?
Elderly
What do chief cells do?
-Regulate free (ionized) calcium via parathyroid hormone (PTH) secretion
MOA of chief cells:
- Increase osteoclast activity
- Increase small bowel absorption of Ca and P
- Increases renal Ca reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
A patient has excess PTH due to a disorder of the paraythyroid gland itself. What is this called?
Primary hyperparathyroidism
What is the most common (and the rest) cause of Primary Hyperparathyroidism:
- Parathyroid adenoma (>80%)
- other causes: sporadic parathyroid hyperplasia and parathyroid carcinoma are less common
What is a parathyroid adenoma?
It is a benign neoplasm, usually involving one gland.
What most often results from a parathyroid adenoma?
-Asymptomatic hypercalcemia. Howeve,r may present with consequences of increased PTH and hypercalcemia (Nephrolithiasis, Nephrocalcinosis, CNS disturbances, Constipation, ACUTE PANCREATITIS, Osteitis fibrosis)
Lab results for a patient come back as follows;
Increased serum PTH, Increased Serum Ca, Decreased serum Phosphate, INCREASED URINARY cAMP, and INCREASED SERUM ALKALINE PHOSPHATASE.
What do they have?
Parathyroid adenoma causing prmary hyperparathyroidism
What is the treatment for a parathyroid adenoma
Surgical removal of affected gland.
What do we call the disease resulting in excess production of PTH due to a disease process extrinsic to the parathyroid gland?
Secondary Hyperparathyroidism
What is the most common cause of Secondary Hyperparathyroidism?
Chronic renal failure
Patient presents with the following lab findings:
Incr PTH, Dec Serum Calcium, Incr Serum Pi, and inc alkaline phosphatase. What do they have?
Secondary Hyperparathyroidism
What is a Trousseau sign, and in what condition would we find it?
Sign: Fill BP cuff on arm and get spasm
-Get it in Hypoparathyroidism due to low serum Ca causign muscle spasms
What is a Chvostek Sign and where do we see it?
- Tap facial nerve –> get muscle spasm
- See this in Hypoparathyroidism secondary to low Ca
DiGeorge Syndrome will result in what?
Hypoparathyroidism (b/c no thyroid or parathyroid due to failure of 3rd/4th pouch
What will be the PTH and serum Ca levels in labs for a patient diagnosied with hypoparathyroidism?
PTH: Decreased
Ca: decreased
What causes Pseudohypoparathyroidism and how does it differ from the real thing?
- Is due to end-organ resistance to PTH [DEFECT IN Gs]
- Labs = hypocalcemia with INCR PTH levels
- Autosomal dominant form is associated with short stature and short 4th and 5th digits
Pancreatic Beta cells produce _____ and are located _____
Insulin. Located in the center of the islets of Langerhans
Summarize the effects of insulin
Major anabolic hormone
- upregulates insulin-dependent glucose transporter protein (GLUT4) on skeletal muscle and adipose tissue (glucose uptake by GLUT4 decreases serum glucose)
- Increased glucose uptake by tissues leads to increased glycogen synthesis, proteins synthesis and lipogenesis.
Pancreatic alpha cells secrete ______. The 2 processes it stimulates are:
Glucagon.
Opposes insulin in order to increase blood glucose levels via glycogenolysys and lipolysis
Hyperglycemia caused by an insulin deficiency is what metabolic disorder?
Type I Diabetes Mellitus
What causes a Type I Diabetes Mellitus?
- Autoimmune destruction of beta cells by T lymphocytes (Type IV hypersensitivity)
- Characterized by INFLAMMATION OF ISLETS (lymphocytes)
- Associated with HLA-DR3 and HLA-DR4
- Autoantibodies against insulin are often present (sign of damage) and may be seen years before clinical disease devleops
- Characterized by INFLAMMATION OF ISLETS (lymphocytes)
Describe the risk for Diabetic Ketoacidosis in DM-I
- Characterized by excessive serum ketones
- Often arises with stress (infection); epinephrine stimulates glucagon secretion –> increases lipolysis
- Increased lipolysis leads to increased free fatty acids
- Liver converst FFAs to ketone bodies (Beta-hydroxybutyric acid and acetoacetic acid.Those 2 = hallmark of Diabetic ketoacidosis
S&S of Diabetic ketoacidosis:
- Hyperglycemia (>300 mg/dL); anion gap metabolic acidosis and hyperkalmeia
- Present with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone)
What is the treatment for Diabetic Ketoacidosis:
Fluids (corrects dehydration from polyuria), insulin, and replacement of electrolytes (k)
A patient presents with a metabolic disorder characterized by hyperglycemia and end-organ insulin resistance. Which disorder is it?
Type 2 Diabetes Mellitus (DM-2)
How is obesity related to DM-2?
Obesitity leads to DECREASED NUMBERS OF INSULIN RECEPTORS on skeletal muscle and addipose tissue.
Describe insulin levels if DM-2 in regards to time:
Insulin levels are increased early in disease.
Later, insulin deficiency develops due to beta cell exhaustion. Histology reveals AMYLOID DEPOSITION IN THE ISLETS.
Explain Dx in DM-2
-Measuring glucose levels (nml = 79-120 mg/dl)
-Radom glucose >200
Fasting glucose >126
Glucose tolerance test with a serum glucose level >200 mg.dL 2 hours after glucose loading
Explain the risk for Hyperosmolar non-ketotic coma in DM-2
High glucose (>500) mg/dL leads to life-threatening diuresis with hypotension and coma. Ketones are absent due to small amounts of circulating insulin [enough to counter the effects of the glucagon
Where does the atherosclerosis associated with Diabetes come from?
Nonenzymatic glycosylation (NEG) of the vascular basement membrane. NEG of large and medium sized vessels leads to atherosclerosis and all of its wonderful complications.
What is the leading cause of death among diabetics?
Cardiovascular disease (brought on by NEG).
What happens if NEG of small vessles (arterioles) occurs?
Leads to hyaline arteriolosclerosis
- Involvement of renal arterioles leads to glomerulosclerosis, resulting in small, scarred kidneys with a granular surface
- Preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury with microalbuminuria that eventually progresses to nephrotic syndrome –> Characterized by Kimmelsteil-Wilson nodules in glomeruli
Where does HbA1c come from?
NEG of hemoglobin produces glycated hemoglobin (HbA1c) - a marker of glycemic control
Explain osmotic damage in Diabetes
- Glucose freely enters into Schwann cells, pericytes of retinal blood vessles, and the lens.
- ALDOSE REDUCTASE converts glucose to SORBITAL, resulting in OSMOTIC DAMAGE
- Leads to peripheral neuropahty, impotence, blindness, and cataracts; diabetes is the leading cause of blindness i the developed world.
VIPomas, Somatostainomas, Gastrinomas, Insulinomas, and Tumors of islet cells are all what type of disorder?
Pancreatic endocrine neoplasms
Tumors of islet cells are often associated with what else?
Often a component of MEN 1 along with parathyroid hyperplasia and pituitary adenoma
What is an insulinoma?
- Pancreatic endocrine neoplasm:
- Presents as EPISODIC hypoglycemia with mental status changes that are relieved by administration of glucose.
How do you diagnosis an Insulinoma?
Decreased serum glucose levels (<50), increased insulin, and INCREASED C-PEPTIDE
What is a Gastrinoma?
- Pancreatic endocrine neoplasm:
- Presents as treatment-resistant peptic ulcers (Zollinger-Ellison Syndrome)
- Ulcers may be multiple and can extend into the jejunum
What is a Somatostatinoma?
- A pancreatic Endocrine neoplasm
- Presents as Achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin -CCK)
What is a VIPoma?
- A pancreatic Endocrine neoplasm
- Secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria
What are the 3 layers of the Adrenal cortex - and what does each produce?
Glomerulosa - mineralocorticoids - aldosterone
Fasciculata - glucocorticoids - cortisol
Reticularis - sex steroids - testosterone
What syndrome is characteristic of excess cortisol?
Cushing Sydnrome
A patient presents with muscle weakness with thin extremities, Moon facies, buffalo hump, truncal obesity, adbominal striae, HTN, Osteoporosis, and immune suppression. What do they have?
Cushing Syndrome
How is a diagnosis of Cushing syndrome made?
Increased 24-hour urine cortisol levels
What causes HTN in Cushing Syndrome?
Cortisol increases alpha1-receptors on arterioles. Increase teh effect of Ne
How does immune suppression occur in Cushing syndrome?
- Inhibition of Phospholipase A2 -> no arachidonic acid metabolites (needed for inflammation)
- Inhibits IL-2 - T-cell growth factor
- Inhibits release of histamine from mast cells
What will happen to a patient on long term exogenous corticosteroids?
- Will lead to bilateral adrenal atrophy
- Steroids suppress ACTH secretion (negative feedback)
- Can develop Cushing syndrome
Primary adrenal adenoma, hyperplasia, or carcinoma can lead to why syndrome?
Cushing Syndrome
-Leads to atrophy of the uninvovled adrenal galnd
What will an ACTH-secreting pituitary adenoma do?
Can cause Cushing syndrome:
-Leads to bilateral adrenal hyperplasia
Paraneoplastic ACTH secretion (e.g. SMALL CELL CARCINOMA OF THE LUNG) can cause what?
Cushing Syndrome:
leads to bilateral Adrenal hyperplasia
How do you differentiate an ACTH-secreting pituitary adenoma from a Paraneoplastic ACTH secretion?
High-dose dexamthasone (cortisol analog):
- SUPPRESSES ACTH production by a pituitary adenoma (cortisol levels decrease) - Fails to suppress ectopic ACTH production by a small cell lung carcinoma (cortisol levels remain high)
What is Conn Syndrome?
Excess aldosterone
Patient presents with HTN w/ Hypernatreamia, hypokalemia, and metabolic alkaosis. What do they have?
Conn syndrome/Hyperaldosteronism
What causes primary hyperaldosteronism
Most commonly due to an adrenal adenoma
-less common: sporadic adreanl hyperplasia, adreanl carcinoma
What characterizes primary hyperaldosteronism?
High aldosterone, low renin
high BP downregulates renin via negative feedback
What is/characterises secondary hyperaldosteronism
Seen with activation of the renin-angiotensin system
Characterized by high aldosterone and HIGH renin
Define Congenital adrenal hyperplasia {CAH]
Excess sex steroids with hyperplasia of both adrenal glands
What is the most common form of CAH
Inherited 21-hydroxylase deficiency
What does 21-hydroxylase do?
- Is required for the production of aldosterone and corticosteroids.
- if it is not there - steroidogeneisis is predominately shunted toward sex steroid production.
- Deficiency of cortisol leads to increased ACTH secretion (no negative feedback), which results in bilateral adrenal hyperplasia
A patient presents with salt wasting (w/ hyponatremia, hyperkalemia, hypovolemia). Also havea life-threatening hypotension.
If female: Clitoral enlargement.
If male: precocious puberty
What do they have?
21-hydroxylase deficieny leading to CAH
- Salt wasting due to lack of aldosterone
- Hypotension due to lack of cortisol
- Sex features due to excess androgens
If presentation is similar to 21-hydroxylase deficiency, but lacks the aldosterone symptoms (so just hypotension, clitoral enlargement/precious puberty). What do they have?
11-hydrxylase deficieny
How would a 17 hydroxylase deficiency present?
No cortisol –> no ACTH –> bilateral adreanl hyperplasia.
Excess mineralocorticoids
No sex steroids
What is Waterhouse-Friderichsen syndrome?
An acute adrenal insufficiency (lack of adrenal hormones.
Characterized by hemorrhagic necorsis of the adrenal glands classically due to DIC in youn children with N. meningitidis infection
- Lack of cortisol exacerbates hypotension, often leading to death
What is Addison Disease?
Chronic adrenal insufficiency - due to progressive destruction of the adrenal glands.
-Common causes: autoimmune destruction (most common in west), TB (developing countries), metastatic carcinoma)
A patient presents with hypotension, hyonatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation, vomiting and diarrhea. What do they have?
Addison disease (Chronic adrenal insufficiency)
What type of cells make up the adrenal medulla?
Neural crest-derived chromaffin cells
-main physiologic source of catecholamines (epi, nor-epi)
What is a pheochromocytoma?
A tumor of chromaffin cells
Patient presents with episodic hypertension, headache, palpitations, tachycardia, and sweating. What does he have?
Pheochromocytoma
How is a Pheochromocytoma diagnosed?
increased serum metanephrines and increased 24-hour urine metanephrines and vanillylmandelic acid (VMA)
How is a Pheychromocytoma treated?
Surgical excision
- Phenoxybenzamine (irreversible alpha-blocker) is administered perioperatively to PREVENT A HYPERTENSIVE CRISIS
Pheochromocytoma rule of 10s….
10% bilateral
10% gamilial
10% malignant
10% located outside of the adreanl medulla (BLADDER WALL OR ORGAN OF ZUCKERKANDL at inferior mesenteric artery root)
How is Pheochromocytoma associated with MEN 2A?
- Medullary carinoma of thyroid
- Pheo
- Parathyroid adenoma
How is Pheochromocytoma associated with MEN 2B?
- Medulary carcinoma of thyroid
- Pheo
- Mucosal ganglio neuroma (espeically in oral mucosa)
How is Pheochromocytoma assoicated with Von Hippel-Lindau disease:
Autosomal dominant
Loss the von-HL tumor suppressor gene
-Increased risk of hemangioblastoma of cerbellum
-renal celll carcinoma and pheyochromocytoma
Pheochromocytoma is associated with NF-1. What is it?
Neurofibromatosis type I
