LECTURE NOT FIRST AID: Endocrine I Flashcards
What leads to a craniopharyngioma? Who gets them?
These slow growing benign intracranial tumors derive from Rathke’s pouch. They present with headache, visual disturbances, pituitary ischemia, and death due to mass effect.
It presents in both ages, children aged 5 - 15, and in adults 65+
What is Adamantinomatous craniopharyngioma?
This is the most common variant of craniopharyngioma, and can be cystic or solid in form (the cystic form contains a thick-yellow brown fluid).
Histology of Adamantinomatous Craniopharyngioma
Stratified Squamos epithelium with peripheral palisading.
Compact lamellar keratin known as “wet keratin” surrounds it
What is papillary craniopharyngioma?
These account for 10% of craniopharyngiomas and are seen more often in adults than children.
Both this and the adamantinomatous version both have low recurrence values.
What hormones are released from the posterior pituitary and what do they do?
ADH - Increases free water reabsorption on the kidney collecting duct. Also increases smooth muscle tone around arterioles throughout the body
Oxytocin - Increases uterine smooth muscle contraction during labor. Stimulates contraction of around the lactiferous duct for milk production
Where are posterior pituitary hormones synthesized and stored?
Posterior pituitary hormones are synthesized in the hypothalamus and stored in axon terminals within Herring Bodies, stored eosinophilic secretory material.
Hormones are released into secondary capillaries.
DI vs SIADH
Discuss clinical features and lab values comparing them
DI - There is hypothalamic undersecretion (in central) or normal levels with unresponsive kidneys (Nephrogenic)
We see low ADH activity and low urine osmolality
SIADH - Total body water increased without edema due to either drugs increasing ADH or other CNS diseases. These patients have cerebral edema and neurologic dysfunction due to hyponatremia.
We see high ADH activity and high urine osmolality
Anterior pituitary hormones are released from:
Acidophils and basophils, directly into hypophyseal veins.
What do acidophils release
Somatotrophe - Growth Hormone
Lactotrope - Prolactin
What do basophils release?
Corticotrope - ACTH
Gonadotrope - FSH/LS
Thyrotrope - TSH
Histology of acidophils and basophils?
They all have purple centers under microscope.
Acidophil - Red cytoplasm
Basophil - Blue cytoplasm
Chromophobe - Clear cytoplasm
Histology of pituitary adenoma
Bland monomorphic densely packed cells
How does lactotrophic adenoma present? In who?
Most commonly detected in women ages 20 - 40
Clinically, we see amenorrhea, galactorrhea, infertility, loss of libido
What drug can we use for lactorophic adenoma and why does it work?
All pituitary adenomas can result in hyperprolactinemia by blocking dopamine release (Prolactin inhibiting factor).
Bromocriptine, a dopamine agonist, may be used for nonsurgical management
Somatotrophic adenoma releases what?
Growth hormone causes production of Insulin-like growth factor (IGF-I) from the liver.
Stimulation of progenitor cells throughout the body, most conspicuous at growth plates and skeletal muscles.
What do somatotrophic adenomas lead to?
Gigantism - Increase GH before epiphyses have closed. We see prominent musculoskeletal enlargement. INFANTS
Acromegaly - Increase GH after epiphyses have closed. Skin and soft tissue growth with enlarged jaw, broadened face, and elongation/thickening of the hands and feet. ADULTS
Discuss corticotropic adenomas and what they lead to
These guys release ACTH, leading to Cushing Syndrome due to cortisol production in the adrenal gland
Discuss Thyrotropic Adenomas and what they lead to
Where does Calcitonin come from and what does it do?
Comes from C cells of the thyroid and decreases blood Ca++
5 signs of hypothyroidism
- Cold intolerance
- bradycardia
- heart failure
- high lipids
- lethargic
5 causes of hypothyroidism
- Los of thyroid tissue
- Hypothalamic failure
- Cretinism
- Hashimoto Thyroiditis
- Granulomatous Thyroiditis
Discuss the pathway that causes cretinism and what it leads to
Iodine deficiency causes a decrease in T4 which leads to poor brain and growth development, leading to mental retardation and dwarfism in infants.
Discuss the histology of hashimoto thyroiditis
Dense lymphocytic infiltrate with germinal centers +/- Hurthle cells
Discuss the course of Hashimoto thyroiditis in the clinic
Painless, but on testing, we see radioactive iodine uptake diminished. Females get this 20x more often than males
Lab test for Hashimoto Thyroiditis
Anti-Thyroglobulin and Anti-thyroid peroxidase
What causes granulomatous thyroiditis, also known as DeQuervain Thyroiditis?
Upper respiratory infection/cytotoxic T-cell mediated condition.
Again, more common in females like Hashimoto’s, but only 4x as much instead of 20x as much
Clinical course of granulomatous thyroiditis?
Unlike hashimotos, this is painful.
Thyroid enlargement is seen, and as before radioactive iodine uptake is diminished.
Histology of Granulomatous Thyroiditis
Early: Patchy, microabscesses
Later: Damaged follicles, lymphocyte aggregates, macrophages transforming into multinucleated giant cells, all of this leading to fibrosis
5 Signs and symptoms of hyperthyroidism
- Heat intolerance
- Tachycardia and arrhythmias
- Increased sympathetic tone
- Tremor
- Ocular changes/lid lag
5 causes of hyperthyroidism
- Grave’s Disease
- Toxic multinodular goiter
- Hyperfunctioning (Toxic) Adenoma
- Iodine induced thyrotoxicosis
- Thyrotropic pituitary adenoma (secondary hyperthyroidism)
Lab findings for hyperthyroidism
Decreased TSH (although in secondary we see increased)
Increased Free T4
Increased T3
In Graves Disease we see ____ radioactive iodine uptake
Increased
Key clinical feature of Graves Disease
Exopthalmos (TSH receptors in extraocular muscles)
What causes the hyperthyroidism we see in Grave’s Disease
Autoantibodies to the TSH receptor cause activation (Thyroid Stimulating Immunoglobulin)
Histology for Graves Disease
Crowded Tall columnar follicular cells with papillary infolding +/- scalloping
What histology do we see with multinodular goiter?
Irregular nodules, colloid-rich follicles, +/- hemorrhage, Ca++, and some cystic changes
Discuss the histology of the thyroid gland
Thyroid follicles surrounded by C-Cells. The lumen of the thyroid follicle is lined by follicular cells.
The interior of the thyroid follicle contains colloid, where we see T3 and T4
What neoplasms do we see in the thyroid gland based on location?
Follicular cells - Follicular adenoma, Follicular carcinoma, papillary carcinoma
C-Cells - Medullary carcinoma
What do we see under histology for papillary carcinoma?
- Intranuclear pseudoinclusions
- Nuclear grooves
We see cleared out nuclei referred to as Orphan Annie Eyes
How do we differentiate between follicular adenoma and follicular carcinoma?
In follicular adenoma, we see well-differentiated follicles.
In follicular carcinoma, we see follicles with loss of colloid
Four C’s of Medullary carcinoma?
- C-cells derived neoplasm
- Calcitonin producing
- Congo Red (amyloid) positive
- CEA (Carcinoembryonia Antigen) is elevated
Neoplastic C-Cells secrete what?
A dense eosinophilic matrix (amyloid)
Discuss the releasing pathway of parathyroid hormone
Low concentration of calcium in the blood causes the release of PTH, which causes a decrease in the loss of calcium in the urine and efflux of calcium from bone.
It causes an increased concentration of calcium in the blood, which inhibits further production of PTH
Clinical manifestations of hyperparathyroidism
Painful bones, renal stones, abdominal groans, psychic groans (depression)
Histology of Adenoma and how often we see it
Bland monomorphic chief cells with small, round, central nuclei. We will also see decreased adipocytes
These account for 85-90% of primary hyperparathyroidisms
Histology of Primary hyperplasia and how often we see it
Similar to Adenoma, but may be diffuse or multinodular
These account for 5-10% of primary hyperparathyroidisms and involves multiple PT glands
Histology of parathyroid Ca and how often we see it
Cytology unreliable, requires invasion or mets.
These account for
What are MEN-1 and MEN-2
Mutation to calcium-sensing receptor gene causing familial hypocalciuric hypercalcemia
What is secondary hyperparathyroidism?
Any condition that gives rise to chronic hypocalcemia. The primary cause is renal failure
Chemical causes of secondary hyperparathyroidism
- Increase phosphate causes decreased serum calcium.
- Decreased a-1-hydroxylase causes decreased active vitamin D
- Both stimulate the PTH production
Other causes include low dietary Calcium or a Vitamin D deficiency
Histology of secondary hyperparathyroidism and organ sequelae that we may also see
Parathyroid glands are hyperplastic (increased chief cells and decreased adipocytes)
Metastatic calcification may be present in the lungs, heart, stomach, and blood vessels.
Treating Secondary hyperparathyroidism
Patients often respond to Vitamin D and phosphate binding agents
What clinical complications do we see with hypoparathyroidism
- Hypocalcemia
- Seizures
- Tetany
- Mental Status changes
- Cardiac Arrhythmias
- Prolonged QT syndrome on EKG
Autoimmune polyendocrine syndrome Type I vs. Type II
APS1
- Autosomal Recessive
- AIRE Gene (21 q22.3)
- Adrenalitis
- Hypoparathyroidism
- Hypogonadism
- Candidiasis
APS2
- HLA Types: DQ or DRB
- Adrenal insufficiency
- Hypothyroidism or Type I Diabetes
Discuss how the hypothalamus leads to hormone release in the adrenal cortex
Hypothalamus releases corticotropin-releasing hormone. This hormone reaches the anterior pituitary gland and causes release of ACTH. ACTH causes the Adrenal cortex to release 3 different hormones:
- Aldosterone from the Z.G.
- Cortisol from the Z.F.
- DHEA from the Z.R.
What are the functions of the three hormones released from the adrenal cortex
- Aldosterone - Regulates salt and water balance in the body
- Cortisol - Regulates carbohydrate metabolism, immune system and maintains blood pressure
- DHEA - Regulates the biosynthesis of androgen and estrogen sex steroids
Based on what hormones we know are coming from what portions of the adrenal cortex, what diseases are associated with what areas of the adrenal cortex?
- Z.G. - Hyperaldosteronism
- Z.F. - Cushing Syndrome
- Z.R. - Adrenogenital/Virilizing Syndromes
What is Conn Syndrome?
Primary Hyperaldosteronism
Increase production of aldosterone that causes hypertension due to retention of Na+ and decreased renin activity (usually idiopathic, can be a neoplasm)
We also note a loss of K+ from the urine.
Signs and symptoms of cushing syndrome
- Weight gain
- Moon face
- Central obesity
- HTN
- Buffalo hump
- Striae, typically on belly
What leads to Adrenogenital/Virilizing Syndroms?
21-Hydroxylase deficiency
Contrast Waterhouse-Friderichsen syndrome and Addison Disease
WFS - An acute condition of adrenocortical insufficiency (hypoadrenalism) where sepsis is caused by encapsulated bacteria (usually N.Meningiditis) leading to hemorrhagic/ischemic loss of adrenal glands.
AD - A chronic condition that presents with hyperpigmentation, weight loss and hypotension
Deciding between an adrenal adenoma and an adrenal carcinoma can be difficult. Under histology, what can guide our decision making?
If we see a wel ldefined, bright yellow tumor that is eosinophilic with vacuolated cytoplasm, we think adrenal adenoma.
A large hemorrhagic/necrotic tumor with variable anaplastic cells under histology is indicative of adrenal carcinoma.
Discuss pheochromocytoma and where we find it?
The chromaffin cells of the medulla produce epinephrine and norepinephrine. A tumor of these cells is termed a pheochromocytoma.
These patients will have episodic hypertension and headaches.
What gene mutations will we see with pheochromocytoma and what lab tests will we get?
Genes: MEN-2A, MEN-2B, NF1, VHL
Lab: Metanephrine and Vanillomendelic Acid (VMA)
Function of the pineal gland
Pinealocytes produce melatonin, a hormone that helps to regulate the wake/sleep cycle and menstral cycle.
Endocrine vs. exocrine pancreas
Endocrine is going to secrete into the blood, so insulin, glucagon and somatostatin are gonna come from this part.
The exocrine pancreas is going to release outside of the body (remember your GI tract? Technically outside of the body!). Zymogens and digestive enzymes for the GI tract are released by this part.
What three cells do we find in the pancreas and what do they release.
Alpha cells - Glucagon - Stimulates an increase in blood sugar levels, thus opposing the action of insulin
Beta cells - Insulin - Regulates metabolism of carbs/fat, esp. the conversion of glucose to glycogen, which lowers the blood glucose level
Delta Cells - Somatostatin - Inhibits the secretion of other hormones such as glucagon, insulin, and gastrin.
What is ketoacidosis?
Insulin deficiency or resistance causes glucose utilization to not function in adipose and muscle, leading to the fat lysing itself and releasing fatty acids and muscle lysing proteins off of itself. This causes a mixture of hyperglycemia (amino acids stimulate gluconeogenesis) and DKA (fatty acids increase ketogenesis).
Plasma glucose (since it isn’t being used by the organs, it stays here) exceeds renal capacity, leading to osmotic diuresis.
What renal complications do we worry about with diabetes?
- Amyloidosis of islet cells
- Diffuse and nodular glomerulosclerosis
- Nephrosclerosis
- Renal Hyaline arteriolosclerosis
What is an insulinoma?
Tumor of Beta cells, this is the most common islet cell tumor. These are monotonous cells with a low mitotic rate and lots of amyloid.
Symptoms arise due to hypoglycemia - Confusion, stupor, coma
What is a glucagonoma (struggle bus here)
Alpha cell tumor
Causes mild skin rash and DM
What is a VIPoma?
Delta cell tumor
Patient has severe watery diarrhea, hypokalemia, and achlorhydria
Discuss the tumors that fall into the category of MEN I - Wermer Syndrome
Pituitary Adenoma, Pancreatic Islet Cell Adenoma, and parathyroid adenoma fall into this category.
Compare MEN IIA and MEN II B
MEN IIA and MEN IIB both involve medullary thyroid carcinomas and pheochromocytomas.
IIA, like I, involves the parathyroid Adenoma, as well as a primary hyperparathyroidism
IIB has ganglioneuromas and neurofibromas.
