Endocrinology Flashcards
What is the most common pituitary adenoma?
Prolactinoma
Why does prolactinoma cause decreased libido in men and amenorrhea in females?
Because prolactin inhibits the release of GnRH
Why does GH adenoma cause DM II?
Because GH decreases glucose uptake into cells
What is pituitary apoplexy?
Bleeding into a pituitary adenoma
Sheehan syndrome
Pituitary gland doubles in size during pregnancy but its blood supply doesn’t increase. During childbirth, if the mother loses a lot of blood, the pituitary can be susceptible to ischemia. Presents as failure to lactate and loss of pubic hair
How does Sheehan syndrome present?
Failure to lactate and loss of pubic hair.
What causes empty sella syndrome?
Herniation of arachnoid/CSF into the sella causing destruction of the pituitary.
What is seen on water deprivation test in central diabetes insipidus?
Water deprivation fails to increase urine osmolality
Anterior cystic midline neck mass that moves with swallowing
Thyroglossal duct cyst
Most common site of ectopic thyroid tissue
Tongue
How does thyroid hormone increase BMR?
Increases Na/K ATPase
How does thyroid hormone increase HR?
Increases beta-1 receptors
What does excess thyroid hormone do to cholesterol and glucose levels?
Hypocholesterolemia. Hyperglycemia (increased gluconeogenesis/glycogenolysis).
What causes exophthalmos and pretibial myxedema in Graves’ disease?
Fibroblasts in eye and on the shin have TSH receptors, and secrete excess glycosaminoglycans in response to excess TSH.
Scalloping of colloid
Graves’ disease
What is myxedema?
Hypothyroidism - causes weight gain, enlarged tongue, deepening of voice (laryngeal edema), muscle weakness, cold intolerance.
Genetic association with Hashimoto thyroidtis
HLA-DR5
1 cause of thyroiditis where iodine levels are sufficient
Hashimoto - hyperthyroidism that progresses to hypothyroidism
2 antibodies seen in Hashimoto thyroiditis
Antithyroglobulin and antimicrosomal antibodies
Antimicrosomal antibodies
Hashimoto thyroiditis
Antithyroglobulin antibodies
Hashimoto thyroiditis
Formation of germinal centers of the thyroid
Hashimoto thyroiditis
What are Hurthle cells?
Intensely eosinophilic metaplasia seen in Hashimoto thyroiditis
Histology of Hashimoto thyroiditis
Chronic inflammation with formation of germinal centers and Hurthle cells (intensely eosinophilic metaplasia)
Granulomatous thyroiditis following a viral infection
Subacute (deQuervain’s) Granulomatous thyroiditis. Thyroid will be very tender, pain “marches” across thyroid.
Very tender thyroid with pain marching across it
Subacute (deQuervain’s) Granulomatous thyroiditis.
Hard as wood thyroiditis
Reidel fibrosing thyroiditis
Describe the findings in Subacute (deQuervain’s) Granulomatous thyroiditis
Granulomatous thyroiditis following a viral infection. Thyroid will be very tender, and pain will “march” across thyroid.
Describe the findigns in Reidel fibrosing thyroiditis
Hard as wood thyroid - nontender
Young patient with hard as wood thyroid and dyspnea. What happened?
Fibrosis from Reidel fibrosing thyroiditis has locally invaded the airway. Seen in YOUNG patients (vs. anaplastic carcinoma which does the same thing in OLD patients).
Describe the findings in iodine uptake studies in Graves disease
Increased
Describe the findings in iodine uptake studies in nodular goiter
Increased
Describe the findings in iodine uptake studies in cancer
Decreased (cold)
How do you biopsy the thyroid?
Fine needle aspiration (biopsy will cause it to bleed like crazy).
What is the hallmark of follicular adenoma of the thyroid?
Cells surrounded by a fibrous capsule - does not invade capsule!
What are the 4 types of thyroid cancer?
Papillary- psammoma bodies, increased risk with irradiation. Orphan Annie eye nuclei, nuclear grooves. Spreads to cervical nodes. Excellent prognosis. Follicular - encapsulated, but invades through capsule (FNA can’t tell it from follicular adenoma). Spreads hematogenously. Anaplastic -seen in older people. Invades locally (can cause dysphagia). Poor prognosis. Spindle cells. Medullary- MEN 2A, 2B, RET oncogene mutation. Malignant cells in an amyloid stroma. Calcitonin is a marker.
1 risk factor for development of papillary thyroid CA
Radiation
Bx of a thyroid mass shows nuclei with a central white clearing
Papillary carcinoma of the thyroid (orphan Annie eyes)
Bx of a thyroid mass shows nuclei with nuclear grooves
Papillary carcinoma of the thyroid
How does papillary CA of the thyroid spread?
Lymphatics (cervical nodes)
Orphan Annie eyes nuclei
Papillary carcinoma of the thyroid
Bx of a thyroid mass shows psammoma bodies
Papillary carcinoma of the thyroid
What distinguishes a follicular adenoma from a follicular carcinoma of the thyroid?
Both are surrounded by a capsule. Follicular carcinoma invades through the capsule, adenoma is contained within the capsule
Why is FNA limited in diagnosis of follicular CA of the thyroid?
Because you need to see the tumor invading through the capsule to call it carcinoma. Adenoma is surrounded by a capsule but it doesn’t invade it.
How does follicular CA of the thyroid spread?
Hematogenously (other carcinomas spreading through blood: RCC, HCC, choriocarcinoma)
Medullary CA is a neoplastic proliferation of…
C cells (why you use calcitonin as marker)
What is a marker for medullary CA of thyroid?
Calcitoninnnnnnnnnnnnjnnkscsnkncnnnnnnnnnnasdcleeesadccmxxxxxleopeorplllodadflloldafdscdmcamdckdnwaddddeededddded
What deposits as localized amyloid in medullary thyroid CA?
Calcitonin
Malignant thyroid tumor cells in an amyloid stroma.
Medullary thyroid CA
Medullary thyroid CA is associated with what 2 genetic conditions?
MEN 2A, 2B (deletion of RET oncogene)
What oncogene is deleted in MEN 2A and 2B?
RET oncogene
RET oncogene mutation
Familial medullary CA of the thyroid - MEN 2A, 2B
Patient has RET oncogene mutation. What procedure should they undergo?
Prophylactic thyroidectomy to reduce the chance of medullary thyroid CA.
Thyroid CA that invades locally
Anaplastic (seen in older people vs. Reidel thyroiditis that occurs in young people)
Thyroid biopsy shows spindle cells
Anaplastic CA - very poor prognosis.
Explain the MOA of parathyroid hormone on bone
Activates osteoblasts, which activate osteoclasts to break down bone
How does increased PTH cause acute pancreatitis?
High calcium is an enzyme activator
Why does alkaline phosphatase increase with increases in PTH?
Because osteoblasts are turned on by PTH, producing alkaline phosphatase. Osteoblasts then activate osteoclasts.
What is the #1 cause of secondary hypoparathyroidism?
Renal failure - decreased vitamin D = decreased calcium = increased PTH.
What causes pseudohypoparathyroidism?
Kidney resistance to PTH - defect in Gs protein.
Patient has hypocalcemia, increased PTH levels, short 4th and 5th digits. Dx?
Pseudohypoparathyroidism - Albright’s hereditary osteodystrophy. Autosomal dominant.
What is Chvostek’s sign? What causes it?
Tapping of facial nerve causing contraction of muscles - caused by hypocalcemia (hypoparathyroidism).
What is Trousseau’s sign? What causes it?
Occlusion of brachial artery with BP cuff causing carpal spasm - caused by hypocalcemia (hypoparathyroidism).
SSX of hyperparathyroidism.
Cystic bone lesions, hypercalcemia, hypophosphatemia, increased urinary cAMP
Anatomically, where are beta cells located in the islets?
In the center
HLA association with type I DM
HLA DR3 and DR4. Need to see inflammation of the islets.
How does obesity cause type II DM?
Decreased # of insulin receptors on peripheral tissues.
Histology of type II DM
Amyloid deposition in islets
What is the feared complication of type II DM?
Hyperosmolar non-ketotic coma - high glucose levels cause life threatening diuresis. Ketones are absent because the patient is still releasing some insulin.
What happens with non-enzymatic glycosylation of large/medium sized vessels in a diabetic patient?
Atherosclerosis (CVD, non-traumatic amputations)
What happens with non-enzymatic glycosylation of small vessels in a diabetic patient?
Hyaline arteriolosclerosis (especially in the kidney - preferential involvement of efferent arteriole).
What happens with non-enzymatic glycosylation of hemoglobin in a diabetic patient?
HbA1c
What causes neuropathy in diabetics?
Schwann cells are not insulin dependent. In DM, they take up sugar and aldose reductase converts them to sorbitol, leading to osmotic damage.
What cells are damaged in DM to cause blindness?
Pericytes of retinal blood vessels - aldose reductase converts sugar to sorbitol, pericytes die.
How do cataracts form in DM?
Glucose taken into cell, converted by aldose reductase to sorbitol, causes accumulation of crystallin proteins and cataracts.
Components of MEN 1
Pancreatic endocrine tumor; Parathyroid hyperplasia; Pituitary adenoma
Components of MEN 2A
Parathyroid tumors; Pheochromocytoma; Medullary thyroid cancer
Components of MEN 2B
Oral ganglioneuroma; Medullary thyroid CA, Pheochromocytoma; Marfan habitus
What MEN is associated with a Marfan habitus?
2B
What MEN is associated with oral ganglioneuroma?
2B
What MEN is associated with VIPoma?
1
What MEN is associated with insulinoma?
1
What MEN is associated with gastrinoma?
1
What MEN is associated with pheochromocytoma?
2A, 2B
<p>What MEN is associated with pituitary tumors?</p>
<p>1</p>
what connects the tongue toe the thyroid during development?
thyroglossal duct
normally disappears but may persist as pyramidal lobe of the thyroid
What is the normal remnant of the thyroglossal duct?
Foramen cecum
Where is the most common extopic thyroid tissue site?
tongue
how would a thyroglossal duct cyst present?
An anterior midline neck mass that moves with swallowing
How would a branchial cleft cyst present?
persistent cervical sinus - lateral neck mass
what controls cortisol secretion in a fetus?
ASTH and CRH from fetal pituitary and placenta
What is the most common tumor of the adrenal medulla in adults?
Pheochromocytoma
What is the most common tumor of the adrenal medulla in children?
Neuroblastoma
Where does the left adrenal gland drain?
Left adrenal to the left adrenal vein to the left renal vein to the IVC
Where does the Right adrenal gland drain?
Right adrenal to the right adrenal vein to the IVC
What hormones are secreted from the posterior pituitary?
ADH and oxytocin
What nucleus from the hypothalamus makes ADH?
Supraoptic nucleis
What nucleus from the hypothalamus makes oxytocin?
Paraventricular nucleus
What is the posterior pituitary derived from?
Neuroectoderm
What is the anterior pituitary derived from?
Oral ectoderm (Rathke’s pouch)
Which hormones share a similar alpha unit?
TSH, FSH, LH and hCG
Which subunit of a hormone determines its specificity?
Beta subunit
what hormone is secreted by each of the pancreatic islets and where are they located?
alpha = glucagon = peripheral beta = insulin = central delta = somatostatin = interspersed
Name two things that can increase ADH levels
Nicotine and opiates
Name three things that can decreased ADH levels?
Ethanol, ANP, and decreased serum osmolarity
What is the role of FSH in males and females?
Males - stimulate spermatogenesis
Females - follicular development and stimulates granulosa cells
What is the role of LH in males and females?
Males - stimulate testosterone production via leydig cells
females - stimulates ovulation and forming of the corpus luteum, acts on theca lutein cells to make estrogen and progesterone
What hormones can inhibit FSH?
Inhibin or constant GnRH release
What hormones can inhibit LH?
Progesterone or testosterone or constant GnRH release
Which hormones are developed from POMC?
Pro-opiomelanocortin = ACTH, MSH, and Beta endorphins
What hormone stimulates and inhibits prolactin release?
Stimulated by Thyroid releasing hormone and inhibited by dopamine
How can you differentiate between a person with an insulinoma or exogenous insulin use?
Exogenous insulin use will not result in an increase of C-peptide
an insulinoma will cause an increased in C-peptide
Does insulin cross the placenta?
no
Describe how glucose regulates insulin release?
Glucose enters the beta cells via GLUT-2 channels. The ATP generated by glucose metabolism (glycolysis) closes K+ channels and depolarizes the beta cell membrane.
This leads to the opening of voltage gated Ca2+ channels which leads tot he secretion of insulin
Describe GLUT-1 channels
These are insulin independent channels - found on RBCs and the brain
Describe GLUT-2 channels
Bidirectional channels - found on Beta islet cells, liver, kidney and small intestine
Describe GLUT 4 channels
Insulin dependent channels - found on adipose tissue and skeletal muscle
note that obesity DECREASES the number of these channels
Describe GLUT-3 channels
located on neurons and in the placenta
Describe GLUT-5 channels
Responsible for fructose uptake in the GI tract
Name 3 things that increased insulin?
Hyperglycemia, growth hormone, Beta-2 agonists
Note that GH increases insulin resistance leading indirectly to increased insulin secretion
Name 3 things that decrease insulin?
Hypoglycemia, somatostatin and alpha-2 agonists
what does the brain depend on in times of starvation?
glucose under normal circumstances and ketone bodies in starvation
Name the catabolic functions of glucagon?
Glycogenolysis, gluconeogenesis
Lipolysis and ketone production
Name three things that inhibit glucagon?
insulin, hyperglycemia, and somatostatin
Name two hormones that somatostatin inhibits from the pituitary?
Growth hormone and thyroid stimulating hormone
How does prolactin inhibit ovulation in females or spermatogenesis in males?
By inhibiting GnRH
What is the function of prolactin?
Stimulates milk production
how does prolactin inhibit its own secretion?
by promoting dopamine release from the hypothalamus
What is the function of growth hormone?
Stimulates linear lgrowth and muscle mass through IGF-1/Somatomedin secretion.
Also increases insulin resistance (diabetogenic)
What is another name for growth hormone?
Somatotropin
What will the lab values be in a patient with 17-alpha hydroxylase deficiency?
Increased mineralcorticoids, decreased cortisol and decreased sex hormones
patient will have hypertension and hypokalemia
What will the lab values be in a patient with 21 hydroxylase deficiency?
decreased mineralocorticoids, decreased cortisol and increased sex hormones
Patient will have hypotension, hyperkalemia , increased renin activity and volume depletion
What will the lab values be in a patient with 11 beta-hydroxylase deficiency?
Decreased aldosterone, increased 11-deoxycorticosterone, decreased cortisol and increased sex hormones
The patient will have hypertension
What will the physical presentation be of a female patient (XX) with 17-alpha hydroxylase deficiency?
Externally phenotypic female with normal internal sex organs. She will lack secondary sex characteristics
What will the physical presentation be of a male patient (XY) with 17-alpha hydroxylase deficiency?
He will have decreased DHT levels leading to pseudohermaphroditism (variable, ambiguous genitalia; undescended testes)
What will the physical presentation be of a patient with 21-hydroxylase deficiency?
masculinization leading to pseudohermaphroditism in females
Recognized in little boys as salt wasting and early in little girls due to decreased development
What will the physical presentation be of a patient with 11 beta hydroxylase deficiency?
Masculinization
What is the only steroid that’s water soluble and is sulfated?
Dehydroepiandrosterone (DHEA)
how does cortisol maintain blood pressure?
Upregulating alpha 1 receptors on arterioles so they are more sensitive to norepinephrine and epinephrine
What effect does cortisol have on fibroblasts?
inhibits fibroblasts - this is why you see striae, due to poor collagen synthesis
Why does cortisol have anti-inflammatory/immunosuppressive effects? (5)
- inhibits production of leukotrienes and prostaglandins
- inhibits leukocyte adhesion leading to neurophilia
3 blocks histamine release from mast cells - Reduces eosinophils
- blocks IL-2 production
What effect does chronic stress have on cortisol?
Induces prolonged secretion
maybe this is why you’re getting fat?
What is meant by permissive action?
A phenomenon where one type of hormone must be present before another hormone can act
Give an example of two hormones that act by permissive action
cortisol is permissive on catecholamines and glucagon.
Thyroxine is permissive on growth hormone
Where is PTH secreted from?
Chief cells of the parathyroid
Does PTH have an effect on osteoclasts or osteoblasts?
Osteoblasts - PTH acts on osteoblasts to increased their secretion of MCSF and RANKL which increases the conversion of osteoclastic precursors to mature osteoclasts –> bone break down and increased serum calcium
Name the 4 effects of PTH
- increased bone resorption of calcium and phosphate
- increased kidney reabsorption of calcium in the distal convoluted tubule
- decreased reabsorption of phosphate in the proximal convoluted tubule
- increased 1,25-OH2D3 (calcitriol) production by stimulating the kidney to make 1 alpha hydroxylase
What effect does 1 alpha hydroxylase have?
made by the kidney in response to PTH to convert Vitamin D to its active calcitriol form
What are the lab values when PTH is high?
increased serum calcium, decreased serum phosphate and increased urine phosphate
Why does magnesium have an effect on PTH?
It can hit the same receptor that calcium does
How can magnesium effect PTH levels?
Slightly decreased magnesium will increase PTH secretion
large decreases in magnesium leads to decreased PTH secretion
Name 4 things that decrease magnesium levels?
- diarrhea
- aminoglycosides
- diuretics
- alcohol abuse
What is the source of Vitamin D?
D3 comes from sun exposure in the skin
D2 is ingested from the plants
Both are converted to 25-OH in liver and to 1,25-OH2 (active form) in the kidney via 1 alpha hydroxylase
What can you see with vitamin D deficiency?
in kids you can get rickets and in adults you can get osteomalacia
What is 24,25-(OH)2 D3 ?
inactive form of Vitamin D
Where is calcitonin secreted from?
Parafollicular cells (C cells of the thyroid)
these are neural crest derived!
What is the role of calcitonin?
Calcitonin opposes actions of PTH. Not important in normal calcium homeostasis though
What is the function of calcitonin? and how is it regulated?
Calcitonin decreases bone resorption of calcium and it’s regulated by increased serum calcium
which endocrine hormones signal via cGMP?
ANP and NO
What happens in a male if they have increased sex hormone binding gobulin?
Sex hormone binding globulin binds to sex hormone so increased amounts will lower the free testosterone in males leading to gynecomastia
What happens in a female is they have decreased sex hormone binding globulin?
In women, decreased sex hormone binding globulin raises free testosterone leading to hirsutism
note that sex hormone binding globulin levels increase during pregnancy
What are the 4 B’s of the T3 functions?
Brain maturation
Bone growth
Beta adrenergic effects
Basal metabolic rate increased
What are the beta adrenergic effects that T3 has?
increased beta 1 receptors in the heart leading to increased cardiac output, HR and SV and increased contractility
How does T3 increase the basal metabolic rate?
by increasing the Na/K ATPase activity leading to increased O2 consumption, RR and body temperature
when do you see increased thyroid binding globulin?
in pregnancy or with OCP use
note that estrogen increases TBG
what converts T4 to T3 in the peripheral tissue?
5’-deiodinase
What does the peroxidase enzyme do?
Responsible for oxidation and organification of iodide as well as coupling of MIT and DIT
What does Methimazole do? What does Propylthiouracil do?
Methimazole inhibits peroxidase only.
Propylthiouracil inhibits both peroxidase and 5’-deiodinase
What is the Wolff-Chaikoff effect?
excess iodine temporarily inhibits thyroid peroxidase leading to decreased iodine organification leading to decreased T3/T4 production
What is the number one cause of cushing’s syndrome?
exogenous steroids
Name 3 endogenous causes of cushing’s syndrome
Cushing’s disease - due to ACTH secretion from pituitary adenoma, has increased ACTH
Ectopic ACTH - from nonpituitary tissue making ACTH, has increased ACTH
Adrenal cause - adenoma, carcinoma, nodular adrenal hyperplasia, has decreased ACTH
A patient takes a dexamethasone suppression test: they have decreased cortisol with low dose dexamethasone and low dose cortisol with high dose dexamethasone; what do they have?
nothing they are normal
A patient takes a dexamethasone suppression test: they have elevated cortisol with a low dose dexamethasone test but it is suppressed with high dose dexamethasone test - what do they have?
ACTH pituitary tumor
A patient takes a dexamethasone test: They have elevated cortisol with both a low dose and an elevated dose of dexamethasone - what are the two possible causes and how do you differentiate between them?
They have either an ectopic ACTH producing tumor (high ACTH) or a cortisol producing tumor (low ACTH)
use ACTH levels to determine where it is coming from
What are the findings with cushing’s syndrome?
BAM CUSHINGOID Buffalo hump Amenorrhea Moon facies Crazy Ulcers Skin changes HTN Infections Necrosis of the femoral head Glaucoma (and cataracts) Osteoporosis Immunosuppression Diabetes
A patient presents with Conn’s syndrome - what is the defect?
Primary hyperaldosterone due to an aldosterone secreting adrenal adenoma or adrenal hyperplasia
What are the findings in a patient with primary hyperaldosteronism?
Hypertension, hypokalemia, metabolic alkalosis and LOW PLASMA RENIN
may be bilateral or unilateral
What is the treatment for a patient with primary hyperaldosteronism?
Surgery! recommended for adrenal adenoma
and/or spironolactone
Why do you have a metabolic alkalosis in primary hyperaldosteronism?
You are peeing out potassium and hydrogen gets secreted with it. and also with the decreased potassium, the K/H exchanger on cells is leading to a further decrease of H+ in order to put K+ out into the body
Name 5 possible causes of secondary hyperaldosteronism
renal artery stenosis, chronic renal failure, CHF, cirrhosis, or nephrotic syndrome
why does secondary hyperaldosteronism occur?
The renals perceive low intravascular volume and as a result they overactivate the renin-angiotensin system
therefore there is HIGH renin
What is the treatment for secondary hyperaldosteronism?
Spironolactone
How does aldosterone work?
Aldosterone increases sodium resorpion at the principal cells in the collecting tubules of the kidney
What is Addisons disease?
Chronic primary adrenal insufficiency
What is Waterhouse Friderichsen syndrome?
Acute primary adrenal insufficiency
Why does Addison’s disease occur?
due to adrenal atrophy or destruction by disease like autoimmune, TB or metastasis.
What are the findings in a patient with Addison’s disease?
Deficiency of aldosterone and cortisol causing hypotension, hyperkalemia, acidosis and skin hyperpigmentation.
Characterized by adrenal atrophy and absence of hormone production from all 3 layers of the cortex (spares medulla)
Why do you see skin hyperpigmentation in a patient with Addison’s disease?
The body is increased ACTH to try to increase the kidney so the increased ACTH is from POMC which also makes MSH
What causes secondary adrenal insufficiency?
Decreased ACTH levels - there is no skin hyperpigmentation or hyperkalemia with secondary adrenal insufficiency
What causes Waterhouse-Friderichsen syndrome?
Adrenal hemorrhage associated with Neisseria meningitides septicemia, DIC and endotoxic shock
What is a pheochromocytoma derived from?
Chromaffin cells (from neural crest)
Name 4 EPO secreting tumors
- Pheochromocytoma
- Renal cell carcinoma
- Hemangioblastoma
- Hepatocellular carcinoma
How do you treat a pheochromocytoma?
tumor surgically removed only after effective alpha and beta blockade is achieved - Irreversible alpha antagonists like phenoxybenzamine must be given first to avoid a hypertensive crisis. Beta blockers are THEN given to slow the heart rate
What will you see elevated in a patient with a pheochromocytoma?
Urinary VMA and plasma catecholamines (NE, D, Epi)
What is a neuroblastoma?
Adrenal tumor in medulla, in kids
can occur anywhere along the sympathetic chain though
What is elevated in a patient with Neuroblastoma? and what differentiates it from a pheochromocytoma?
You will see elevated homovanillic acid in the urine
it’s different from a pheochromocytoma because it occurs in kids and because you won’t see hypertension with it
What oncogene is overexpressed in patients with neuroblastoma?
N-myc
what is a myxedema coma?
extreme form of hypothyroidism - life threatening due to decompensated state - patient will have an altered mental status, hypothermia, bradycardia, hypoventilation, and cardiovascular collapse
can occur in older women who are undiagnosed or undertreated and have a significant stressor
What are the 5 Ps of Cretinism?
Pot-bellied, Pale, Puffy faced child with Protruding umbilicus and Protuberant tongue
Name the thyroid condition: Most common cause of hypothyroidism
Hashimoto’s thyroiditis
Name the thyroid condition: Anti-microsomal antibody
Hashimoto’s thyroiditis
Name the thyroid condition: Hurthle cells, lymphocytic infiltrate with germinal centers
Hashimoto’s thyroiditis
Name the thyroid condition: Moderately enlarged non-tender thyroid, autoimmune disorder associated with HLA-DR5
Hashimoto’s thyroiditis
Name the thyroid condition: Due to severe fetal hypothyroidism
Cretinism
What causes endemic cretinism?
Wherever endemic goiter is prevalent AKA lack of dietary iodine
What causes sporadic cretinism?
Defect in T4 formation or developmental failure in thyroid formation
Name the thyroid condition: very tender thyroid
Subacute de Quervain’s thyroiditis
Name the thyroid condition: Self-limited hypothyroidism often following a flu like illness or a viral infection
Subacute de Quervain’s thyroiditis
Name the thyroid condition: Increased ESR, jaw pain, early inflammation, histology shows granulomatous inflammation
Subacute de Quervain’s thyroiditis
Name the thyroid condition: Thyroid replaced by fibrous tissue and has hypothyroidism
Riedel’s thyroiditis
Name the thyroid condition: Considered a manifestation of IgG4 related systemic disease
Riedel’s thyroiditis
Name the thyroid condition: Fixed hard rock like painless goiter in a patient with hypothyroidism
Riedel’s thyroiditis
Name three drugs that can cause hypothyroidism?
Amiodarone
Tyrosine kinase inhibitors
Lithium
Name the thyroid condition: Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in the TSH receptors leading to increased release of T3 and T4
Toxic multinodular goiter
What is Jod-Basedow phenomenon?
Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete
Name the thyroid condition: Type II non cytotoxic hypersensitivity causing an autoimmune hyperthyroidism with thyroid stimulating immunoglobulins that are mostly IgG
Graves disease
Name the thyroid condition: A patient presents with hyperthyroidism and labs show increased serum T4, T3 and decreased serum TSH but they have increased iodine 123 uptake.
Graves disease
What is a thyroid storm?
Stress induced catecholamine surge leading to death by arrhythmia - seen as a serious complication of Graves disease and other hyperthyroid disorders.
May see increased ALP due to increased bone turnover
How do you treat a thyroid storm?
Beta blockers and prevent with PTU or methimazole
Name the thyroid cancer: Orphan Annie’s eyes, nuclear grooves and psammoma bodies
Papillary carcinoma
Name the thyroid cancer: most common
Papillary carcinoma
Name the thyroid cancer: increased risk with childhood irradiation, but has good prognosis
Papillary carcinoma
Name the thyroid cancer: good prognosis with uniform follicles, can invade through a capsule and spread hematogenously
Follicular carcinoma
How will malignant tumors look on a scan?
Malignant thyroid cancer will never cause hot nodules because they aren’t working like normal tissue
Name the thyroid cancer: associated with RAS mutation or PAX 8-PPAR gamma1 rearrangement
Follicular carcinoma
Name the thyroid cancer: from parafollicular “C” cells secreting calcitonin
Medullary carcinoma
Name the thyroid cancer: Secretes calcitonin
Medullary carcinoma
Name the thyroid cancer: Associated with MEN 2A and 2B - look for RET gene mutation
Medullary carcinoma
Name the thyroid cancer: sheets of cells in an amyloid stroma
Medullary carcinoma
How do you treat medullary carcinoma?
With surgery - medullary carcinoma doesn’t respond to radioactivity because it isn’t a carcinoma of actual thyroid hormone producing cells - it’s the medullary part!
Name the thyroid cancer: undifferentiated tumor in an older patient, poor prognosis
Anaplastic carcinoma
Why type of hypothyroidism has an increased risk of non-Hodgkin’s lymphoma?
Hashimoto’s thyroiditis
A patient has hyperthyroidism - which trimesters of pregnancy should you use what drug?
First trimester - propylthiouracil
2nd and 3rd trimester - Methimazole
What is the most common cause of primary hyperparathyroidism?
adenoma
will see hypercalcemia
What are the findings in a patient with primary hyperparathyroidism?
Hypercalcemia
Hypercalciuria (stones), hypophosphatemia, increased PTH, increased alkaline phosphatase, increased cAMP in the urine
patients may be asymptomatic or presenting with weakness and constipation (groans)
What is osteitis fibrosa cystica?
seen in primary hyperparathyroidism
cystic bone spaces fed with brown fibrous tissue leading to bone pain
What is seen with secondary hyperparathyroidism?
Secondary hyperplasia due to decreased gut calcium absorption and increased phosphate - most commonly seen in chronic renal disease (causes hypovitaminosis D leading to decreased calcium absorption)
What are signs of hypoparathyroidism?
hypOcalcemia = tetany
positive Chvostek’s sign and Trousseau’s sign
What causes hypoparathyroidism?
surgical excision with thyroid surgery, autoimmune destruction, Digeorge’s syndrome
What is pseudohypoparathyroidism?
Albright’s hereditary osteodystrophy - autosomal dominant kidney unresponsibe to PTH
leads to hypocalcemia, shortened 4th and 5th digits and short stature
What are the findings in a pituitary adenoma?
Most commonly due to prolactinoma - will have amenorrhea, galactorrhea, low libido, infertility
also possible bitemporal hemianopia
when you suspect acromegaly - what should you check?
They will have increased serum IGF-1
also have failure to suppress serum GH following an oral glucose tolerance test
Name 4 possible causes of central Diabetes insipidus?
pituitary tumor, trauma, surgery, histiocytosis X
Name 3 possible causes of nephrogenic Diabetes Insipidus?
hereditary or secondary to hypercalcemia, lithium, or demeclocycline
How do you treat central DI?
intranasal desmopressin
How do you treat nephrogenic DI?
Hydrochlorothiazide, indomethacin, or amiloride
What drug can cause SIADH?
Cyclophosphamide
What are the findings in SIADH?
excessive water retention
hyponatremia with continued urinary sodium excretion
urine osmolarity > serum osmolarity
How does the body respond to SIADH?
the body responds by decreasing aldosterone (hyponatremia) to maintain near-normal volume status. Very low serum sodium levels can lead to seizures though
What are the possible treatments for SIADH?
Fluid restriction, IV saline, conivaptan, tolvaptan, demeclocycline
what are 4 super common findings in diabetes?
Polydipsia, Polyuria, polyphagia, weight loss
What does non-enzymatic glycosylation do in diabetes to small vessels?
causes diffuse thickening of basement membranes
why do you get osmotic damage in diabetes?
Due to sorbitol accumulation in organs with aldose reductase and decreased or absent sorbitol dehydrogenase
Why do you get nuropathy in Diabetes?
due to sorbitol accumulation in schwann cells
What does the HBA1c tell you for a diabetic?
The average blood glucose for the prior 3 months
what do you see on histology in patients with type 1 DM?
Islet leukocytic infiltrate
What do you see on histology in patients with Type 2 DM?
Islet amyloid (AIAPP) deposit
why do Type 1 DM get ketoacidosis but Type 2 don’t?
Type 2 still have some insulin on board, but type 1 doesn’t
Insulin prevents lipolysis so without the break down of fat you don’t get ketones or beta oxidation or kussmaul breathing!
How do you get carcinoid syndrome?
Carcinoid tumor that is not just in the GI tract! produces high levels of serotonin which are broken down by the liver before it can cause problems if it occurs in the GI tract only
What are the symptoms of Carcinoid syndrome?
B-FDR Bronchoconstriction Flushing Diarrhea Right sided valvular diseae
What will you see in the urine of a pt with carcinoid tumor?
Increased 5-HIAA
they will also have a niacin deficiency
How do you treat carcinoid tumor?
Somatostatin analog like octerotide
A patient has a gastrinoma - what will you see?
The stomach will show rugal thickening with acid hypersecretion. They will also have recurrent ulcers
What is MEN1?
PPP
Pituitary, Parathyroid, Pancreatic tumor
What is MEN2A?
PPM
Parathyroid, Pheochromocytoma and medullary thyroid carcinoma
What is MEN2B?
PMM
Pheochromocytoma, Medullary thyroid carcinoma, mucosal neuromas (oral/intestinal ganglioneuromatosis)
A patient presents with hyperglycemia, anemia, venous thrombosis, infections, diarrhea, mental status changes and necrolytic migratory erythema - what is it?
Glucagonoma
A patient presents with DM, cholelithiasis, steatorrhea and hypochlorhydria - what is it?
Somatostatinoma
What are the toxicities seen with insulin?
Hypoglyceamia, very rarely hypersensitivity reactions
Name 3 rapid acting insulin drugs
Lispro, Aspart, Glulisine
Name 1 short acting insulin drug
Regular insulin
Name an intermediate acting insulin drug
NPH
Name 2 long acting insulin drugs
Glargine and Detemir
What drug is a Biguanide?
Metformin
What are the side effects seen with metformin?
GI upset, most severe side effect is lactic acidosis so it’s contraindicated in renal failure
What is the first like therapy in type 2 DM?
Metformin
Name 2 first generation sulfonylureas
Tolbutamide and Chlorpropamide
Name 3 second generation sulfonylureas
Glyburide, Glimepiride, Glipizide
What is the action of sulfonylureas?
Close K+ channel in Beta cells membrane leading to depolarization and therefore triggering of insulin release via increased calcium influx
What patients can benefit from sulfonylureas?
Stimulates release of endogenous insulin in type 2 DM - it requires some islet function so it doesn’t work in Type 1 DM
What are the effects of first vs second generation sulfonylureas?
First - disulfiram like reaction
Second - hypoglycemia
Name two drugs that are Glitazones/Thiazolidinediones
Pioglitaonze and Rosiglitazone
How do Glitazones/ Thiazolidinediones work?
Increase insulin sensitivity in peripheral tissue. They bind to PPAR-gamma nuclear transcription regulator found in the liver, adipose and skeletal muscle
What drugs use a intracellular nuclear receptor target to treat diabetes?
Glitazones/Thiazolidinediones
What are the side effects of Glitazones/Thiazolidinediones?
Weight gain, edema, hepatotoxicity and heart failure
Who can benefit from Glitazones/Thiazolidinediones?
Used as monotherapy in type 2 DM or combined with other agents
Name two drugs that are alpha glucosidase inhibitors
Acarbose and miglitol
How do alpha glucosidase inhibitors work?
Inhibit intestinal brush border alpha glucosidases therefore decreases GI absorption of disaccharides
You get delayed sugar hydrolysis and glucose absorption leading to decreased postprandial hyperglycemia
Who can benefit from alpha glucosidase inhibitors?
Used as monotherapy in type 2 DM or combined with other agents
What are the adverse effects of alpha glucosidase inhibitors?
Gi disturbances like flatulence, diarrhea, abdominal cramping
Name an amylin analog and it’s function
Pramlintide - functions to decrease glucagon, delayed gastric emptying
Who can benefit from using Pramlintide?
both type 1 and 2 DM
Name two GLP-1 analog drugs used to treat diabetes
Exenatide and Liraglutide
How do Exenatide and Liraglutide function?
Increase insulin and decreased glucagon release in type 2 diabetics
They increased Beta cell growth and replication, slow gastric emptying and decrease food intake
What drugs can cause nausea, vomiting and pancreatitis?
Exenatide and Liraglutide
Name 4 DPP-4 inhibitors that can be used to treat diabetes
Linagliptin
Saxagliptin
Sitagliptin
Alogliptin
How do DPP-4 inhibitors work?
Increase insulin and decrease glucagon release in type 2 diabetics
They prolong incretin actions which decreased glucagon secretion and increase insulin secretion and delay gastric emptying
Which diabetic drugs can cause mild urinary or respiratory infections?
DPP-4 inhibitors
Name two drugs that can act as thyroid replacements?
Levothyroxine (T4) and Triiodothyronine (T3)
can use these to treat hypothyroidism or myxedema
When are two times you might use GH as a treatment?
GH deficiency or turner syndrome
List 5 uses for Somatostatin (Octreotide)
Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices
List 4 uses for Oxytocin
Stimulates labor, uterine contractions, milk let-down, controls uterine hemorrhage
Name 1 use for ADH (desmopressin)
Pituitary DI
What would you use Demeclocycline for?
SIADH - it’s an ADH antagonist
What are the side effects of demeclocycline?
Nephrogenic DI, photosensitivity, abnormalities of bone and teeth
What is the mechanism of action for glucocorticoids?
Decreases the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX2
What are some clinical uses of glucocorticoids?
Addison’s disease, inflammation, immune system, asthma
Why is metformin so great, especially for patients on beta blockers?
Metformin doesn’t cause hypoglycemia, which can be masked by beta blockers