Thyroid Disorders Flashcards
1
Q
What is the etiology of Hypothyroidism
A
Decrease in thyroid function
Primary:Peripheral(thyroid) disorder
T3/T4 decreased
TSH increased
CausesL Autoimmune: Hashimoto thyroiditis
surgery, irradiation, radiotherapy
Drugs: lithium, iodide, p-aminosalicyclic acid
Iodine deficiency
Congenital hypothyroidism
2
Q
What is the etiology of secondary hypothyroidism
A
central hypothyroidism
*Pituitary disorders-dec TSH, T3/T4 {Pituitary tumor, postpartum pituitary necrosis, trauma & non-pituitary tumors}
*Hypothalamic disorders
dec TRH levels, TSH, T3/T4
{tumors, trauma, radiation therapy, or infiltrative diseases
3
Q
What is the alter physiology hypothyroidism
A
slowing of thyroid
accumulation of glycoaminoglycan —>myxoedema
4
Q
What is the alter physiology hyperthyroidism
A
catabolism
SNS
impaired reproductive sys
goitre—> hyperplasia & hypertrophy
Compression by goitre
trachea—.dyspnoea, oesophagus, dysphagia
Recurrent laryngeal N—> Hoarseness of voice
SVC syndrome: facial & arm swelling
Cervical sympathetic plexus—> Horner
5
Q
Clinical presentation of hypothyroidism
A
Cool and pale skin
yellowish discoloration
dry skin
dry, brittle, coarse hair & brittle nails
less sweating
nonpitting edema(myxedema)
MSK:
muscle weakness, cramps, and myalgias; carpal tunnel syndrome, hyporeflexia, dyspnoea
GI: constipation, weight gain
Neuro: depression, cognitive dysfunction
Metabolic:hyponatremia
Eye: Periorbital edema
Hyperprolactinemia
amenorrhea; menorrhagia
CVS: reduced cardiac output:reductions in heart rate(bradycardia)
HTN, hypercholesterolemia
hematogical: Macrocytic (megaloblastic)
6
Q
Subclinical hypothyroidism levels
A
mildly inc TSH, normal T3/T4
7
Q
Primary hypothyroidism
A
inc TSH
dec T3
dec or normal
8
Q
secondary and tertiary hypothyroidism
A
dec TSH
dec T4
9
Q
Thyroid antibody testing
A
TPOAb
TgAB
TRAbs{Hashimoto}
10
Q
Euthyroid sick syndrome/non thyroidal disease
A
dec T3
T4 & TSH normal
11
Q
alters thyroid hormone synthesis and release by inhibibitors
A
IL-1, Il-6, TNF-alpha, and IFN beta
Disrupts target tissue response of thyroid hormones»> TBG reduction or thyroid receptor down regulation due to protease clevage
12
Q
Most common mutation in pituitary adenoma involves
A
Activated G protein mutations
13
Q
Pt presents with white fluid from breast not associated with pregnancy causes
A
Pituitary adenoma Dopamine antagonist injury to stalk
14
Q
H/A Bitemporal visual loss, Past History of adrenal gland surgery ACTH very high
A
Nelson syndrome
15
Q
Fatigue, dizziness, weight loss, reduced muscle mass/muscle weakness, low blood sugar and low blood pressure
A
Low ACTH
16
Q
Irregular menses, loss of libido
A
Low FSH/LH
17
Q
Cold intolerance, weight gain, brittle nails & hair irregular menses, decreased growth in children
A
TRH
18
Q
Stunted growth, increased body fat decreased muscle mass
A
GHRH
19
Q
Obese hypertensive lady with hypopituitarism, enlarged sella pituitary gland height loss
A
Empty sella syndrome
20
Q
H?A, blurring of peripheral vision, sudden hypopituitarism
A
Pituitary apoplexy
Pituitary hemorrhage
21
Q
Failure of migration of neurons olfactory to hypothalamus»> Delayed puberty, Testis is <1-2 mL volume & ANOSMIA GnRH def
A
Kallman syndrome
KAL 1 gene mutation
22
Q
Abnormalities in growth hormone receptors (GHR) due to mutations Low GH & IGF-1 low
A
Larron syndrome
23
Q
Bitemporal hemianopsia
A
Optic chiasm
24
Q
Increases prolactin
A
Dopamine block and high TRH, Prolactinoma
25
Any blood disorder that can cause pituitary infarction
SCD
26
Galactorrhea loss of lateral vision headache
Prolactinoma
27
Grossly machine oil like secretions seen
Craniopharynigioma
28
Child, brain tumour squamous cells seen on histopathology
Craniopharyngioma
29
Pituitary tumour tumous shows GNAS mutation IGF 1 RAISED
Somatroph adenoma GH
30
Tumour is a derivative of Rathkes pouch child calcified tumour
Craniopharyngioma
31
Most common mutation in pituitary adenoma involves
Activated G protein mutations
32
Pr presents with white fluid from breast not associated with pregnancy causes
Pituitary adenoma Dopamine antagonist injury to stalk
33
Pt on Haloperidol what clinical symptom expected, Why??
Increase prolactin dopamine antagonist
34
Headaches, Bitemporal visual loss, Past History of adrenal glands surgery ACTH very high
Nelson syndrome
35
Desmopressin
V2 agonist; Central diabetes insipidus; Enuresis; Hemophilia A; Von Willebrand disease
A/E: GI, hyponatremia
36
Oxytocin
Activates Gq-IP-DAP-Ca2+
Uterine tone, induction labor, PPH
A/E: fetal distress, uterine rupture
37
Bromocriptine
Cabergoline
Activates dopamine
D2 receptions,
Suppresses the prolactin & GH
Hyperprolactinemia, acromegaly, parkinson disease
A/E: GI, orthostatic hypotension, psychosis, vasospasm
38
Follitropin alpha
Activates FSH receptors
Controlled ovarian stimulation, infertility due to hypogonadotropic, hypogondadism in men(MHH)
A/E: multiple pregnancies,gynecomastia in men
39
hCG
Agonist at LH receptors
Initiation of final oocyte maturation and ovulation during controlled ovarian stimulation, MHH
A/E: depression
40
Leuprolide
GnRH agonist. Increase LKH & FSH secretions with intermittent administration. Reduced LH and FSH secretion with continuous admin.
Ovarian suppression, controlled ovarian stimulation, central precocious puberty, prostate cancer, endometriosis, breast cancer
A/E: H/A, nausea
41
Ganirelix
Blocks GnRH receptors, reduces endogenous LH, FSH
Prevention of premature LH surge during controlled ovarian stimulation
A/E: H/A, nausea
Contraindications: pregnancy
42
Mecasermin
R IGF-1
IGF-1 deficiency that is not responsive to exogenous GH
Hypoglycemia, intracranial hypertension, hepatotoxicity
43
Somatropin: Recombinant Human GH (rhGH)
• Mechanism of action: Activates JAK tyrosine kinase and STAT → IGF-1 →
longitudinal bone growth → GH → reduces insulin sensitivity → IGF-1 →
glucose uptake → In patients with GH receptor mutation → rIGF-1 →
hypoglycemia
• Peak levels occur in 2–4 hours, and active blood levels persist for
approximately 36 hours.
44
Somatropin: Recombinant Human GH (rhGH)
Clinical use:
Growth: Growth failure in paediatric patients associated with:
• Growth hormone deficiency
• Prader-Willi syndrome
• Turner syndrome
• Chronic renal insufficiency pre-transplant
• Small-for-gestational-age with failure to catch up by age 2 years
• Noonan syndrome
• Short stature homeobox-containing gene (SHOX) deficiency
• Idiopathic short stature, pituitary dwarfism
• Improved metabolic state, increased lean body mass, sense of wellbeing
• Growth hormone deficiency in adults
• Increased lean body mass, weight, and physical endurance
• Wasting in patients with HIV infection
• Improved gastrointestinal function
• Short bowel syndrome in patients who are also receiving specialized nutritional support
45
Adverse Effects and Contraindications: GH
Pseudotumor cerebri, slipped capital femoral epiphysis, scoliosis, edema,
hyperglycaemia, asphyxiation in severely obese patients with Prader-Willi
syndrome
• Patients with turner syndrome → risk of otitis media
• Pancreatitis, gynecomastia, and nevus growth
• Peripheral edema, myalgia, and arthralgia
• Contraindications:
• Malignanc
46
Mecasermin
Uses:
A/E:
▪ Recombinant human IGF-1
▪ Uses:
▪ Treatment of severe IGF-1 deficiency that is
not responsive to GH
▪ Laron syndrome is the most common cause
of growth hormone insensitivity and
caused by mutations in the GH receptor
gene
▪ Adverse effects:
▪ Hypoglycemia
▪ Intracranial hypertension, lipohyp
47
Pharmacotherapy of Growth Hormone Excess
▪ Gigantism or acromegaly
▪ Transsphenoidal surgery, radiation, and drugs
▪ Somatostatin analogs: Octreotide, Lanreotide
▪ Growth hormone receptor antagonist: Pegvisomant
▪ Dopamine agonist: Cabergoline
48
Octreotide, Lanreotide
▪ It is not identical to SS, only 8 amino acids,
▪ Mechanism of action: Somatostatin analog → Inhibiting GH,
IGF-1, TSH, glucagon, insulin, serotonin, VIP, secretin, motilin,
pancreatic polypeptide, LH, and gastrin release
49
Uses & A/E Octreotide, Lanreotide
Uses:
• Acromegaly, gigantism
• Carcinoid tumor, gastrinoma, glucagonoma
• Insulinoma, VIPoma, ACTH secreting tumor
• Secretory diarrhea, portal hypertension
• Somatostatin receptor scintigraphy
• Control of bleeding from esophageal varices
Adverse effects:
Nausea, vomiting, abdominal cramps, flatulence, steatorrhea,
biliary sludge, gall stones, hypertension, peripheral edema,
alopecia, bradycardia, vitamin B12 deficiency
50
Pegvisomant
Pegvisomant is a GH receptor antagonist
MOA: Pegvisomant binds to the GH receptor
→ blocking the binding of endogenous GH
→ prevents activation of JAK-STAT signaling
or stimulate IGF-1 secretion→ normalizes
serum IGF-1
Uses:
• Acromegaly
• Alternative for use in patients not
respond to SST
Adverse effects:
• Diarrhea, antibody formation,
elevation of liver transaminase,
infection
• Lipohypertrophy
51
Hypothalamic-Pituitary-Gonadal Axis
GnRH → Gq-IP3-PLC-DAG-Ca→
LH & FSH → Ovaries & Testis →
androgens, estrogens, &
progesterone
Preovulatory surge of estrogen
→ ↑ GnRH
52
Drugs having Agonist or Antagonist
Effects of Gonadotropins
• Hypothalamus
• GnRH
• Agonist
• Gonadorelin
• GnRH receptor agonist
• Leuprolide
• GnRH receptor antagonist
• Ganirelix
• Anterior pituitary
• Gonadotropins
• FSH
• Follitropin
• LH
• hCG
• FSH & LH
• Menotropin
53
Gonadotropins [FSH & LH] & Human
Chorionic Gonadotropin
FSH, LH, and hCG– Alpha subunit, LH & hCG share beta subunit.
Signaling pathway: Camp
Menotropins [human menopausal gonadotropin-hMG]
• Both FSH & LH, follicle development in women
• Follitropin alfa and beta
• Recombinant FSH
hCG, Choriogonadotropin alfa, Lutropin alfa [withdrawn in 2012]
Identical to LH
54
Uses of Gonadotropins
Infertility in women
• Anovulation that is secondary to hypogonadotropic
hypogonadism, polycystic ovary syndrome, and other causes
• FSH & LH → induction of ovulation
• Assisted reproductive technology
• Invitro fertilization
• FSH [menotropins or follitropin] each day, for 9 to 12 days →
to stimulate maturation of the ovarian follicle → On the day
after the last dose is given, a single dose of an LH
preparation such as chorionic gonadotropin is administered
to induce ovulation followed by insemination or oocyte
retrieval for in vitro fertilization procedures.
55
Uses of Gonadotropins
Infertility in men
Menotropins → spermatogenesis
hCG [LH] → testosterone production
Cryptorchidism - hCG
Adverse effects:
Multiple pregnancies and the ovarian hyperstimulation
syndrome [OHSS
56
Gonadotropin Releasing Hormone Agonists
GnRH: Gonadorelin, leuprolide, nafarelin, histrelin, etc.
Pharmacokinetics: SC, IV, nasal spray, depot preparations, pellets
Mechanism of action:
GPCR – IP3 → pulsatile administration → ↑ FSH, LH
→ continuous administration → down regulation of GnRH
receptors → ↓ FSH, LH → ↓ estrogen, testosterone
Uses:
• Advanced prostate cancer, breast cancer, endometriosis,
and uterine fibroids, central precocious puberty, suppress
premature LH surge in the treatment of infertility.
Adverse effects:
• Hot flashes, depression, diminished libido, generalized pain,
vaginal dryness, and breast atrophy
57
Gonadotropin Releasing Hormone Antagonists
GnRH antagonists: Ganirelix, Cetrorelix, & degarelix
Mechanism of action:
• Competitive antagonist at GnRH receptors → ↓ IP3 → ↓ FSH
& LH
Uses:
• Infertility, inhibits premature LH surge in women ovarian
hyperstimulation
• Prostate cancer: ↓ Testosterone
Adverse effects:
• Hypersensitivity, allergy and anaphylaxis
Contraindications:
• Pregnancy
58
Gonadotropin Releasing Hormone Antagonists
Pregnancy testing.
• The placenta produces significant amount of hCG
• Detected in maternal urine few days after first missed
menstrual period
• Estimate plasma hCG
Timing ovulation
• Urine LH levels on day 10-12
Localization of endocrine disease
• Measurements of plasma LH and FSH → low levels in
hypogonadotropic hypogonadism and hypothalamic or
pituitary disease.
• → high levels → Primary gonadal disease
Male primary hypogonadism
• hCG → stimulates Leydig cell → Testosterone
59
Prolactin & Related Drugs
Prolactin:
• 198 amino acids, anterior pituitary, structurally like growth hormone
• Mammary gland → tissue growth & milk production in the presence of estrogen,
progestin, and other hormones
• Prolactin secreting adenoma & TRH → Hyperprolactinemia → infertility &
galactorrhea → inhibits GnRH → inhibits ovulation in females & spermatogenesis
in males → hypogonadism → osteoporosis
• Dopamine antagonists → hyperprolactinemia
Cabergoline or bromocriptine:
• Activates dopamine D2 receptors → ↓ Prolactin
Uses:
• Hyperprolactinemia, mixed growth hormone and prolactin secreting pituitary
adenoma
Adverse effects:
• Nausea, headache, dizziness, vasospasm, psychosis, etc.
60
Sheehan Syndrome
Pituitary infarction
A history of postpartum hemorrhage
Inability to lactate
Los of all anterior pituitary hormones
61
Drugs Affecting Prolactin Levels
Drugs that block dopamine D2 receptors cause
hyperprolactinemia by blocking the inhibitory effects of
endogenous dopamine on the pituitary cells that release
prolactin.
• The older antipsychotic drugs (e.g., phenothiazines,
haloperidol), with their strong dopamine D2 receptor-blocking
activity, are most likely to be the pharmacologic cause of
hyperprolactinemia.
• This adverse effect is less likely with atypical antipsychotic drugs
(e.g., olanzapine).
• Drugs or drug groups that cause hyperprolactinemia through
mechanisms that are not well characterized include methyldopa
(an antihypertensive), amphetamines, tricyclic and other types
of antidepressants, and opioids.
62
Oxytocin
Posterior pituitary hormone, nonapeptide
Clinical uses:
• To induce & augment labor
• Milk letdown reflex
• To control of uterine hemorrhage after vaginal
or cesarean delivery
Adverse effects:
• Excessive stimulation of uterine contractions
before deliver can cause fetal distress,
placental abruption, or uterine rupture, fluid
retention, hyponatremia, heart failure, seizures,
and death
Contraindications:
• Fetal distress, Prematurity, cephalopelvic
disproportion
Atosiban:
• Antagonist of oxytocin receptor used to
suppress preterm labor [Not FDA approved]
63
Vasopressin (Antidiuretic Hormone; ADH)
ADH: Posterior pituitary hormone
• Release → plasma tonicity or ↓ BP
• Deficiency: central diabetes insipidus
Desmopressin:
• Long acting, intravenously, subcutaneously, intranasally, or orally
MOA:
• V1 of vascular smooth muscle → Gq +PLC +IP3 → vasoconstriction
• V2 of renal tubular cells → Gs + AC → ↑ water permeability &
reabsorption; extra-renally release of factor VIII and von Willebrand
Uses:
• Pituitary diabetes insipidus, nocturnal enuresis, esophageal variceal
bleeding, hemophilia A and von Willebrand disease
Adverse effects:
• Headache, nausea, abdominal cramps, agitation, and allergic
reactions
64
Vasopressin (Antidiuretic Hormone; ADH)
• V1a – vasoconstriction
• V1b – ACTH release
• V2- ADH response
• ↑ vasopressin & hyponatremia → heart failure
• Conivaptan antagonist of V1a and V2 receptors
• Uses: Hypervolemic, euvolemic hyponatremia, SIADH, & heart failure
• Tolvaptan more selective for V2 → ↑ free water clearance → ↓ urine
osmolality → ↑ serum sodium concentrations.
• Use. Autosomal dominant polycystic kidney disease, SIADH,
cirrhosis.
• Demeclocycline & Lithium:
• Demeclocycline and lithium act on the collecting tubule cell to diminish
its responsiveness to ADH, thereby increasing water excretion.
• Both drugs causes nephrotoxicity
65
̄decT3,dec T4, incTSH.
- The thyroid gland itself is under-producing thyroid hormone. TSH goes due to ̄ negative-feedback at hypothalamus + anterior pituitary.
- HY examples are Hashimoto thyroiditis (autoimmune destruction of thyroid gland) and iodine deficiency (insufficient thyroid hormone precursor).
Primary hypothyroidism
66
Secondary hypothyroidism
The thyroid gland is under-producing thyroid hormone due to inadequate stimulation (i.e., the anterior pituitary isn’t producing sufficient TSH).
- HY causes are Sheehan syndrome (ischemic infarction of anterior pituitary postpartum) and pituitary tumors (e.g., prolactinoma, which impinge on and necrose the thyrotropes in the anterior pituitary that produce TSH).
- ̄ TRH from the hypothalamus causing ̄ TSH could be another theoretical cause, but I’ve never seen this assessed. Dec T3, dec T4, dec TSH.
67
TSH- or TRH-secreting tumor causing over-stimulation of thyroid gland.
- Despite the thyroid hormone, TSH can’t be suppressed because there is autonomous secretion from a tumor.
- In theory, hypothalamic / anterior pituitary glandular hyperplasia, or inflammation (autoimmune hypophysitis) could also cause TSH leading to secondary hyperthyroidism. Inc T3/4/TSH
Secondary hyperthyroidism
68
Primary hyperthyroidism
-increased T3,increase T4,decrease TSH.
- The thyroid gland itself is over-producing, causing suppression of TSH.
- HY example is Graves disease (activating-antibody against TSH receptor), toxic adenoma (autonomously secreting nodule), and toxic multinodular goiter (multiple autonomously secreting nodules).
- TSH is suppressed due to negative-feedback at the hypothalamus / anterior pituitary.
69
Aka subacute granulomatous thyroiditis, or just simply subacute thyroiditis.
- Mechanism is viral infection followed by a painful/tender thyroid. There is inflammation of the thyroid gland, which causes the spacing between the cells to increase slightly, allowing for the release of pre-formed thyroid hormone into the blood. Therefore we have ̄ TSH, T3, T4, ̄ 131I uptake.
- The gland is not over-producing thyroid hormone. This is why uptake is not increased.
- Subacute granulomatous thyroiditis can be either hypo- or hyperthyroid. The key detail you need to know is that uptake is always decreased even if the patient is hyper-.
deQuervain thyroiditis
70
Subclinical hypothyroidism
Inc TSH,<—>T3,<—->T4.
- In subclinical hypothyroidism, the patient will be asymptomatic (hence subclinical) and will have normal T3 and T4, despite an elevated TSH.
- Most patients with subclinical do not need to be treated.
- Don’t treat unless TSH >10, patient is pregger, or anti-Hashimoto Abs are +.
71
Drug-induced thyroiditis
Caused by lithium or amiodarone on USMLE.
- Can in theory be hypo-, eu-, or hyperthyroid.
- Will usually present on USMLE as painless hypothyroidism in patient being treated for bipolar disorder (lithium) or started on new anti-arrhythmic (amiodarone).
- Will present with ̄ 131I uptake, where inflammation of the gland can sometimes cause leakage of thyroid hormone into the blood, but the gland itself is not demonstrating increased production of hormone.
72
PTU
Methimazole
73
Lugol’s solution
Potassium iodide
74
What is propranolol MOA, Uses, Kinetics and A/E
75
What drug do you give your pregnant patients with hyperthyroidism?
76
The most common cause of hyperpituitarism is
Anterior lobe pituitary adenoma
