What is acromegaly due to? To what patients?What are the symptoms?
Pit tumor (micro or macro) causing overproduction of GH in adults (middle age)
Symptoms: overgrowth of soft tissues of face (nose and lips), hands, feet, and bones
What is gigantism due to? What are the symptoms?
Macroadenoma causing overproduction of GH in children (before closure of epiphysial endplate in puberty)
Symptoms: incredible height (7-8 feet), and sometimes acromegaly in adulthood
What is pituitary dwarfism due to? What are the symptoms?
Inability of pit to produce enough GH
Symptom: insufficient stature growth
What is Laron dwarfism due to? What are the symptoms?
Special subset of pit dwarfism due to lack of functioning GH receptors
Symptoms: insufficient stature growth and high GH because IGF-1 is not produced
What is wide-range hypopituitarism?
When a patient has a dysfunction of many cell types contained in the anterior pit
Why could macroadenoma cause increase in PRL?
If tumor is really pressing hard it is cutting flow of venous blood from the hypo to pit gland so dopamine is not making it to the pit
Are pit tumors usually cancerous/metastatic?
How do we treat thyroid tumors? What can this damage as collateral?
Radioactive iodide therapy to ablate the tumor
Salivary glands can be damaged also
How is thyroid storm treated during pregnancy? Why?
With PTU only during the first trimester (because it also causes liver damage) and then methimazole
What does eating cassava cause in people from Zaire?
They already are not ingesting enough iodide and by eating cassava they cannot pump iodide into the follicular cells of the thyroid gland, so this causes:
1. Low iodide
2. High amounts of TSH: thyroid gland growth = goiter
What is cretinism due to? Symptoms?
Insufficient amounts of thyroid hormones during development causing short stature and stunted brain development
What is newborn hypothyroidism caused by? How is it treated? Symptoms if not treated?
Inability to make thyroid hormones at birth
Treatment: administer thyroid hormones to prevent cretinism and growth defects (downturned mouth and dead eyes) FOR THE REST OF THEIR LIVES
What is endemic goiter caused by? 3 symptoms?
Not enough iodide in diet
1. Increased TRH
2. Increased TSH
3. Thyroid growth
What is Grave's disease caused by? More prevalent in what patients? Symptoms? Treatment? Side effects?
Autoimmune disease where antibodies (TSI: Thyroid Stimulating Igs) attack the TSH receptor of the thyroid gland stimulating it and causing high thyroid hormone production = hyperthyroidism and sometimes diffuse goiter
More common in women
10% of patients also have
Symptom: big eyes (proptosis), heat intolerance, tremor, weight loss, perspiration, diarrhea, oilier skin
Treatment: perchlorate, thiourea drugs (not PTU), surgery, and radioactive iodine (I131)
Side effects: weight gain
What is Hashimoto's thyroiditis caused by? Symptoms?
Autoimmune disease where antibodies attack thyroglobulin and break down the thyroid gland = hypothyroidism
Symptoms: cold intolerance, weight gain, cold clammy skin, slow reflexes and reactions, constipation
What is the Wolff-Chiakoff effect? How long does it last? Why? What is it often used to manage/prevent (2 things)? In what form?
Short-term effect of excess levels of iodide exerting negative feedback on the production/release of thyroid hormones at the point of thyroglobulin release of T3/T4 (vesicle formation). Relieved after 48 hrs due to increased export of iodide.
Solution of K+I- can be used to:
1. Manage or prevent thyroid storm
2. Decrease size (therefore vasculature) of thyroid and amount of THs
What are the long-term effects of excess iodide levels? Why?
Permanent iodide block and a goiter and hypothyroidism develop probably due to some underlying defect in thyroid
What are the medium-term effects of excess iodide levels? Why? How long does it take cells to recover?
Increased organification leading to increased MIT and DIT but decreased T3/T4 possibly because of decreased T3/T4 content of TGB
Takes cells 7-10 days to recover
What are the 3 types of patients to whom we recommend PTU instead of methimazole?
1. First trimester pregnant women
2. Thyroid storm
3. Allergic to methimazole
What is a thyroid storm? What can it be caused by? What is the main risk? Treatment?
Huge amount of TH entering your system at once.
Can be caused during neck surgery (may or may not involve thyroid), by surgeon causing a huge release by touching the colloid space that has months worth of hormones
Risk: ventricular fibrillation and heart attack. Very dangerous.
Treatment: PTU, lithium, and methimazole
What is a goitrogen?
Food containing TH production/release inhibiting agent
How long does it take for newborn hypothyroidism to be noticed? How come?
Few days because of T4 half life in newborn blood from mother
What other condition is often seen alongside Grave's disease? Why?
70% of patients also have Hashimoto's thyroiditis because different kinds of antibodies are being produced: some will activate some will destroy
People with this type of autoimmune disorder typically do not present with both conditions in full bloom at the same time, but one after the other: symptoms of hyperthyroidism would gradually diminish (except the exophthalmos might need to be surgically corrected) and the symptoms of Hashimoto's hypothyroidism would gradually begin to appear
Can iodide be used to treat hyperthyroidism? When?
Yes, in the short-term
Why does hyperthyroidism cause weight loss and hyperphagia?
Because excess TH causes an increase in the basal metabolic rate causing an increased caloric intake which is then burned fast:
1. Na+ is more permeable so the Na+/K+ ATPase channels are doing more work
2. Gut motility is increased
Why does hyperthyroidism cause heat intolerance? 2 reasons
1. Excess TH increases the basal metabolic rate
2. Excess TH causes an increase in uncoupling proteins: mitochondrial inner membrane proteins channels/transporters that are capable of dissipating the proton gradient generated by NADH-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space. The energy lost in dissipating the proton gradient via UCPs is not used to do biochemical work. Instead, heat is generated.
What does a diffuse goieter mean?
Means the size increase is consistent all around the gland
What does constitutive production of a hormone mean? Eg?
Production without negative feedback.
Eg: endemic goitier
What is virilization?
Masculinization is the biological development of sex differences
What is the effect of the drug metyrapone?
Blocks 11-β-hydroxylase => cortisol/aldosterone decrease
What is a pyrogen?
Substance, typically produced by a bacterium, that produces fever when released into the blood
What causes Cushing's disease? 2 symptoms? 2 prolonged effects? Effect on water retention?
Caused by pituitary adenoma that releases excess ACTH: high cortisol levels
Symptom: purple striae on skin (similar to stretch marks) due to skin proteolysis of collagen and lipolysis in hips, thighs, and butt (not uniform) causing a redistribution of fat
Prolonged effects: insulin resistance and Type 2 diabetes because constant hyperglycemia and free FAs also trigger insulin causing a redeposition in fat store in belly and back of neck (buffalo hump)
Water retention increase: moon facies (puffy and round)
What can excessive water retention lead to?
What causes Cushing's syndrome? Symptoms? Treatment?
Cause is NOT pituitary adenoma but problem with adrenal gland (usually adrenal tumor)
Symptoms: same as Cushing's disease
Treatment: adrenal gland removal
How to diagnose Cushing's disease vs syndrome?
Cushing's disease: high ACTH and cortisol levels
Cushing's syndrome: low levels of ACTH and high cortisol levels
What can patients with very low cortisol experience in time of stress?
Vascular collapse: BP goes to 0, insufficient blood flow and nutrients to the brain, sometimes fatal
What causes Addison's disease? Treatment? Symptoms?
Autoimmune attack on adrenal cortex, which cannot produce cortisol.
Treatment: glucocorticoid replacement therapy
Symptoms: high ACTH, low BP, low blood glucose levels, potential vascular collapse, and very tan skin (palms, feet soles, and gums)
Why do Addison patients have very tan skin?
1. Lack of cortisol causes ACTH levels to rise
2. Breakdown of proopiomelanocortin (POMC) (to create ACTH) also produces α-melanocyte-stimulating hormone (α-MSH)
3. α-MSH stimulates melanocytes in the skin to produce pigment in response to UV
What is the major inhibitor of thyroid hormone production?
What are the 4 competitive inhibitors of the I-/Na+ symporter of the follicular cells of the thyroid gland? What do these inhibit exactly? How?
1. Thyocyanate: SCN-
2. Perchlorate: ClO4-
3. Perrhenate: ReO4-
4. Pertechnetate: TcO4-
Inhibit the UPTAKE of iodine, not the pump itself because they are transported instead (indirect inhibition)
What is diabetes insipidus characterized by?
Low BV and large dilute urine volume
What are the 4 types of diabetes insipidus? What is the treatment for all of them?
1. Central = neurogenic = hypothalamis
Treatment: long-lasting vasopressin agonist (snorted)
What is central/neurogenic diabetes insipidus due to? Overall and 6 causes?
Inability to synthesize or secrete active vasopressin:
1. Metastatic tumor
3. Histiocytosis (immune related)
4. Severe whiplash that severes the pituitary stalk
6. Anatomical defect
What is nephrogenic diabetes insipidus due to?
Inability of kidney to detect vasopressin: usually V2 or aquaporin receptor (AQP2) mutation
What is dipsogenic diabetes insipidus associated with?
Excessive water drinking linked to psychiatric disorders: schizophrenia with over consumption of water
What is gestational diabetes insipidus due to?
Placenta secretes vasopressinase that degrades vasopressin
What is tocolysis?
The delaying or inhibition of labor during the birth process
What drugs can be used to help adoptive breastfeeding? How does each work?
1. Domperidone: blocks pituitary dopamine receptors
2. TRH: directly stimulates lactotrophs (PRL)
3. Metoclopramide/Sulpiride/Chloropromazne: blocks dopamine mediated inhibition of prolactin secretion
What is Rickets caused by? Symptoms?
Vitamin D deficiency causing lack of calcium absorption = soft bones, bone deformation, bow legs, compromised height
What happens when Vitamin D receptors are missing in the body? What disease is this?
Alopecia and oligodontia (lack of teeth)
Why does aspirin have an anti-clotting effect? How does it do this? What is the side product?
Archidonic acid |protaglandin synthase=cyclooxygenase + hydroxiperoxide|⇒prostaglandin H2⇒prostacyclin + thromboxane (potent aggregator of platelets)
Aspirin INHIBITS cyclooxygenase by IRREVERSIBLE binding Ser at active site and acetylating it (side product: salicylate)
What is a common treatment option for inflammatory diseases or organ transplants causing excess levels of CRH? What can be the side effects of this treatment?
Exogenous glucocorticoids to increase appetite and cause negative long feedback loop to hypo
Side effects: elevated glucose can lead to hyperinsulemia and potentially Type 2 diabetes and excessive feeding can lead to increase in fat mass
What types of symptoms can inappropriately high levels of CRH cause?
Cushing's like symptoms
How is CRH related to clinical depression?
Constant high CRH levels drive clinical depression
Other than stress, what other 5 states are associated with an increase in the HPA axis?
1. Anorexia nervosa
2. Excessive exercise
3. Type 2 diabetes
5. Cushing's syndrome
What are 5 disorders associated with a decreased HPA activation?
1. Chronic fatigue syndrome
2. Post-partum depression
5. Rheumatoid arthritis
What is polysystic ovarian disease? Most common symptom? Cause?
Most common reproductive disorder among women of reproductive age.
Most common symtom: infertility
Cause: increase in stress/obesity = increase in cortisol = increase in insulin/IGF-1 = ovaries secrete elevated androgens
How can stress increase risk for heart attack in middle-aged men?
They already have atherosclerotic plaques in the lumen of their vessels so a stressful event or chronic stress can cause even more vasoconstriction in coronary arteries leading to heart attack
How does stress affect cancer?
Chronic stress has been shown to cause a tumor to metastatize in mice studies
Does stress cause cancer?
Describe what happens during beta-cell exhaustion in T2D.
Eating sugary foods all the time causes increase in insulin demand and the beta cells enlarge and burn out (apoptosis) and we also increase our resistance to insulin
Describe what happens during amyloid deposition in T2D.
Amylin is secreted from beta cells with a 1:100 ratio with insulin to slow gastric emptying to promote satiety and prevent post-prandial spikes in blood glucose (decreasing rate of carb uptake) BUT a certain AA sequence of it causes beta-amyloid plaque formations in the beta cells when secreted too much (badly processes and too many of them), which can kill the beta cells and add pressure to remaining cells
What has been found to prevent amyloid plaque formation on beta cells of the pancreas? Why?
Coffee because it contains polyphenols and caffeine metabolites (caffeic acid and chlorogenic acid)
How is ghrelin secretion affected by bariatric surgery?
Why do people who develop Type 2 diabetes keep eating sugary foods?
Because insulin levels rise fast in response to high sugar foods, so you get hungry again very fast
How does cyanide poisoning affect the ETC?
1. Cyanide binds to Fe3+ (ferric iron) in the heme of cytochrome a and a3 in Complex IV, preventing it from accepting electrons
2. Flow of electrons to O2 is blocked as well as all of the previous steps up to NADH oxidation
What is the treatment for cyanide poisoning? Explain how this works.
Amyl nitrite inhalation or IV infusion with NaNO2
Converts oxyhemoglobin to methemoglobin (containing Fe3+), which can then easily bind cyanide and is converted to thiocyanate
What is favism?
Condition caused by lack of G6PD enzyme and foods that have divicine (like fava beans): too many ROS in RBCs and no NADPH to protect the body
Symptoms: anemia, diarrhea, respiratory problems, can be lethal
Treatment: avoid oxidizing agents in diet
These people do not lack ribose-5-phosphate because they can ingest it and they do not lack NADPH for biosynthesis because it can also be produced via conversion of malate to pyruvate
Describe Wernick's encephalopathy.
Characterized by ocular abnormalities, ataxia, and state of global confusion. Commonly (but not exclusively) associated with chronic alcohol abuse.
Cause: Thiamine/vitamin B1 deficiency
Early manifestations include fatigue, irritability,
sleep disturbance, abdominal pain, and anorexia.
Cause: Thiamine=vitamin B1 deficiency
Describe Pyruvate Dehydrogenase Complex Deficiency
X-linked genetic disorder manifested in infancy or later childhood by progressive neural symptoms, including intermittent ataxia, poor muscle tone, abnormal eye movements, or seizure. Patient manifests elevated blood lactate with a normal pyruvate/lactate ratio.
What is hypocalcemia caused by? Symptoms?
Vitamin D deficiency
Circumoral numbness (in mouth), and QT prolongation is noted on ECG
Why are there neuro symptoms associated with dysfunctions of the PDC?
Because brain needs acetyl-CoA to function properly
What is respiratory distress syndrome? Treatment?
Syndrome due to lack of surfactant in premature babies
Treatment: artificial lung surfactant and O2
What can be measured to understand the maturity of the surfactant being produced by a premature baby? Describe the interpretation of the results.
Measure L/S ratio = L-phosphatidylcholine/S-sphingomyelin ratio:
- Normal term pregnancy: >=2
- 1.5-2: 40% chance of developing respiratory distress syndrome
- <1.5: % chance of developing respiratory distress syndrome
What drugs can be used to help adoptive breastfeeding? How does each work?
1. Domperidone/Metoclopramide/Sulpiride/Chloropromazne: blocks pituitary dopamine receptors
2. TRH: directly stimulates lactotrophs (PRL)
What is atosiban? What has been figured out about it?
Oxytocin antagonist that is ineffective at delaying labor because oxytocin only plays a minor role
What are polychromocytomas?
Tumors of the adrenal medulla that over produce epi/norepi
What is going bald the result of? How can it be prevented?
The conversion of testosterone to DHT at the hair follicles
Prevention: block DHT