Endocrinology Flashcards
(96 cards)
1
Q
What is the embryological remnant of the thyroglossal duct?
A
Foramen cecum.
2
Q
What is the most common site of ectopic thyroid tissue?
A
Tongue (lingual thyroid)
3
Q
How do thyroglossal duct cysts present
A
Anterior midline neck mass that moves with swallowing or protrusino of the tongue
4
Q
What hormones does the adenohypophysis secrete?
A
POMC derivatives: beta-endorphins, ACTH and MSH
FSH, LH, TSH, PRL, GH
5
Q
What hormones does the neurohypophysis secrete
A
ADH (vasopressin)
Oxytocin
6
Q
What embryological structures give the two parts of the pituitary respectively?
A
Oral ectoderm (Rathke pouch) = anterior
Neuroectoderm = posterior pituitary
7
Q
What are the 3 zones of the adrenal cortex and what hormones are they responsible for?
A
8
Q
What types of cells are in the adrenal medulla and what do they produce?
A
9
Q
What are the 3 types of cells of the pancreas and what hormones do they secrete?
A
Alpha = glucagon
Beta = insulin
Gamma = somatostatin
10
Q
What hormone does prolactin inhibit?
A
GnRH
11
Q
What hormones does dopamine inhibit?
A
Prolactin
TSH
12
Q
What hormones does somatostatin inhibit?
A
GH
TSH
13
Q
Other name for growth hormone
A
Somatotropin
14
Q
Explain the MoA of the growth hormone pathway and its relationship to glucose
A
GHRH (hypothalamus) –>GH (adenohypophysis)
GH stimulates liver and muscle mass growth through insulin-like growth factor 1 (IGF-1).
Goal of GH = energy preservation (glucose) for vital organs. Therefore, its MoA relies on
A) increasing glucose availabilty to vital organs (decreased glucose uptake - increased insulin resistance)
B) Generating energy from alternative sources: lipolysis, protein synthesis (increased amino acid uptake).
15
Q
What factors induce GHRH secretion?
A
States in which energy preservation is important stimulate GHRH: sleep, exercice, puberty, stress, hypoglycemia
16
Q
What physiologic factors inhibit GHRH secretion?
A
States in which there is already a lot of circulating glucose: Aging, obesity, hyperglycemia
17
Q
Manifestations of excessive GH in adults vs children
A
Adults - acromegaly
Children - gigantism
18
Q
Management of GH excess
A
Somatostatin analogs or surgery for pituitary adenoma
19
Q
Other name for ADH
A
Vasopressin
20
Q
Which organ synthesizes ADH?
A
Hypothalamus - supraoptic and paraventricular nuclei, stored and secreted by the posterior pituitary
21
Q
How does vasopressin work?
A
Insertion of aquaporins in the renal collecting duct.
22
Q
Stimulation vs inhibition of ADH
A
Increased serum volume/decreased osmolality = inhibition of ADH
vice versa
23
Q
What happens to ADH in central diabetes insipidus?
A
ADH is diminished
24
Q
Describe the prolactin pathway (inhibitors, activators)
A
25
True or false - hypothyroidism = increased prolactin secretion
True, if hypothyroidism is primary or secondary because hypothyroid = increased TRH and TRH stimulates prolactin
False if hypothyroidism is tertiary, no because the cause of hypothyroid is then diminished TRH
26
Relationship between dopamine and prolactin
Dopamine is a prolactin antagonist
27
Tell me about the thyroid hormone regulatory pathway
28
Tell me about the relationship between T4 and T3 (which is more predominant where,...)
Thyroid synthesizes mostly T4, such that in the circulation there is T4>T3.
Peripheral tissue 5-deiodinases turn T4 into T3 with rT3 being a byproduct. T3 then carries out the downstream thyroid function.
29
Components of T4 and T3
DIT + DIT = T4
DIT + MIT = T3
30
What is the Wold-Chaikoff effect?
Protective autoregulation mechanism wherein sudden exposure to excess iodine temporarily turns **off** thyroid peroxydase such that T4 and T3 production is halted.
31
What binds thyroid hormone peripherally and what does that result in?
Thyroid binding globulin (TBG).
Bound T4/T3 is inactive.
32
What are the functions of T3?
33
What happens to TBG in pregnancy and OCP use?
Increased, so total T4/T3 is increased in those states.
34
2 causes of decreased TBG
Steroid use, nephrotic syndrome
35
Molecule likely responsible for Graves disease?
Thyroid-stimulating immunoglobulin, which may stimulate follicular cells to increase T4 production
36
Tell me about the PTH pathway
PTH is released from parathyroid glands on the thyroid in response to **indicators of low circulating free calcium ions** (e.g. decreased ionized calcium, increased phosphate or decreased Vitamin D3).
PTH acts on renal tubular cells to A) increase Vit D3 production B) reabsorb more calcium and C) excrete more phosphate
Vitamin D also acts on bone for increased resorption and on the intestine for increased absorption of both calcium and phosphate.
37
Influence of magnesium on PTH
Severe hypomagnesemia can cause hypocalcemia that is resistant to calcium replacement — and only corrects once magnesium is also repleted.
Often seen in alcoholism, malnutrition, chronic diarrhea, or diuretic use.
38
Where is calcitonin produced and released?
parafollicular cells of the thyroid
39
Roles of calcitonin
Decreased bone resorption
40
When is glucagon secreted?
In response to hypoglycemia
41
What is the relationship between insulin and C-peptide?
C-peptide is a byproduct of endogenous insulin release, not seen in iatrogenic hypoglycemia.
42
Insulin synthesis pathway
beta cells of the pancreas
43
Do insulin and glucose cross the placenta?
neonatal hypoglycemia often seen in babies of diabetic mothers due to increased insulin production in the fetus during pregnancyN
44
What is the THE insulin-dependent glucose transporter?
GLUT-4: adipose tissuem striated muscle
Exercise increases GLUT-4 expression
45
Cells with insulin-independent glucose uptake
BRICK LIPS
Brain
RBC
Intestine
Cornea
Kidney
Liver
Islet beta cells
Placenta
Spermatocytes
46
Name GLUT receptors and their function
47
Insulin production by pancreatic beta cells steps
48
Insulin action on insulin-dependent glucose uptake cells steps
49
Stimulation of which receptors decreases release of insulin?
Alpha 2 = decreased insulin
Beta 2 receptors = increased insulin
50
Explain the pathway that is promoted in 17-alpha hydroxylase deficiency
Causes accumulation of precursors in the mineralocorticoid pathway (no glucocorticoid or androgen production).
This results in **incresaed 11-deoxycorticosterone** (pathway of mineralocorticoid production), which acts on the kidneys to **retain salt and water** and **excrete K+**.
Aldosterone is low.
51
Why is aldosterone low in 17-alpha hydroxylase deficiency despite everything being "shifted" toward the mineralocorticoid pathway?
Because aldosterone is mainly synthesized in response to the RAAS pathway stimulation.
In this deficiency, there is increase 11-deoxycorticosterone which increases renal water and sodium uptake (classical symptoms of hypertension). Therefore, the renin pathway is not stimulated and there is no increased aldosterone.
52
How does 17-alpha hydroxylase deficiency manifest in genetic males vs females?
XY individuals: hypertension. appear female (female/ambiguous genitalia, undescended testes). No uterus.
XX individuals: lacks secondary sexual development due to lack of estrogen production.
53
Laboratory findings in 17-alpha hydroxylase deficiency
54
What is the most common enzyme deficiency in congenital adrenal hyperplasia?
21-hydroxylase
55
Explain pathophysiological consequences of 21-hydroxylase deficiency
Enzyme required for synthesis of glucocorticoids and mineralocorticoids.
Deficiency - everything is shifted towards the zona reticularis (androgens).
56
How does 21-hydroxylase deficiency present in biological males vs females
XY: virilization
XX: excess prenatal exposure to androgens = virilization of external genitalia (clitoromegaly, labial fusion...)
Presents in infancy with salt wasting or childhood with precocious puberty.
57
Explain lab findings in 21-hydroxylase deficiency
Decreased mineralocorticoids and cortisol
Increased sex hormones
Increased K+ due to no action of Na+/K+ ATPase in the kidneys
Decreased BP (salt wasting) - increased renin
58
Explain pathophysiological consequences of 11-beta hydroxylase deficiency
Cortisol pathway is blocked and aldosterone production is impossible, but we can still make 11-deoxycorticosterone.
A lot of precursors are still shunted towards the androgen pathway.
59
Explain lab findings in 11-beta hydroxylase deficiency
60
What is the general role of cortisol?
Hormone of stress: goal is to mobilize all energy for fight or flight. Therefore:
* Glucose production: insulin resistance, gluconeogenesis, lipolysis and proteolysis
* Decreased immune and inflammatory responses, and decreased fibroblast activity
* Increased blood pressure
61
Pathway of cortisol secretion
62
True or False: exogenous glucocorticoids can cause reactivation of TB and cadidiasis. If true, how?
True
Blocks IL-2 production
63
Relationship between cortisol and melanocyte-stimulating-hormone
Both MSH and ACTH are POMC derivatives.
When there is low cortisol, there is more ACTH production from POMC and along with that, increased MSH --> melanin
64
Impact of chronic stress on cortisol
Prolonged cortisol secretion
Cortisol resistance
Impaired immunocompetency
Dysregulation of HPA axis
65
3 hormones regulating appetite
Ghrelin
Leptin
Endocannabinoids
66
Ghrelin effects
67
Leptin effects
68
Endocannabinoids effects
69
Tell me about SIADH
Syndrome of inappropriate ADH secretion
Excessive free water retention
Urine osmolality>serum osmolality
**Euvolemic hyponatremia** because body responds to increased water retention with increased ANP and BNP and decreased aldosterone = Na+ secretion. This leads to normalization of the extracellular fluid volume
70
Treatment of SIADH
Fluid restriction (first line)
Salt tablets
IV hypertonic saline
Diuretics
ADH antagonists
71
Causes of SIADH
HEELD-up water
* Head trauma/CNS disorders
* Ectopic ADH (e.g. small cell lung cancer)
* Exogenous hormones (e.g. vasopressin, desmopressin, oxytocin)
* Lung disease
* Drugs (SSRIs, carbamazepine, cyclophosphamide)
72
In SIADH, is the urine dilute or concentrated?
Concentrated
73
In diabetes insipidus, is the urine dilute or concentrated?
Dilute
74
Causes and characterstics of central diabetes insipidus
* Etiology is decreased ADH release
* Causes: idiopathic, brain injury
* Serum osmolality increases (increased water output)
* ADH level decreased
* If administer desmopressin (ADH analog), water is now retained and therefore we see a **significant increase in urine osmolality**
75
Management of diabetes insipidus
Desmopressin - ADH analog
76
Causes and characterstics of nephrogenic diabetes insipidus
Etiology: ADH resistance
Causes: hereditary (V2 receptor mutation), drugs (e.g. lithium, demeclocycline), hypercalcemia, hypokalemia
Serum osmolality: increased (water still excreted)
ADH level: normal or increased
Desmopressin administration makes no difference in urine osmolality
77
What is Sheehan syndrome?
Ischemic infarct of pituitary following severe postpartum hemorrhage.
Pregnancy induces pituitary growth, so it is more susceptible to hypoperfusion.
Presentation: failure to lactate, amenorrhea, cold intolerance - anterior pituitary hormones mainly affected.
78
Most common cause of acromegaly
Pituitary adenoma
79
Equivalent of acromegaly in kids
Gigantism
80
How to make diagnosis of acromegaly
* Increased serum IGF-1 (made in the liver in response to GH)
* Failure of GH suppression following oral glucose tolerance test
* Pituitary mass seen on MRI
81
Hyperthyroidism metabolic symptoms
Symptoms of increased metabolism: weight loss (due to increased Na+/K+ ATPase synthesis = increased basal metabolic rate due to high consumption of ATP)
Increased sweating (more internal heat due to increased BMR and sympathetic stimulation of sweating), heat intolerance
82
Hyperthyroidism skin, nail and hair changes
Skin: warm and moist; peritibial myxedema seen in Graves'
Hair: fine and falling (increased turnover of cells)
Nails: Oncholysis
83
Hyperthyroidism ocular manifestations
Exophthalmos, periorbital edema
Lid lag / retraction due to increased parasympathetic stimulation of the superior tarsal muscle
84
Hyperthyroid MSK manifestations
Thyrotoxic myopathy (proximal weakness, **normal CK**)
Osteoporosis / increased fracture rate because T3 stimulations bone resorption and release of Ca2+
85
Hyperthyroid effects on cholesterol
Increased LDL cholesterol expression = decreased LDL and HDL levels
86
Why does hypothydoidism cause myxedema
Increased glucosaminoglycosans (GAGs) in interstitial space = **generalized non-pitting edema** which raises osmotic pressure and leads to water retention
87
Which increases CK? Hypothyroid or hyperthyroid?
Hypothyroid = muscle breakdown due to impaired clearing of waste products
Hyperthyroid = muscle overuse, but not much breakdown
88
What is the most common cause of hypothyroidism in iodine-sufficient regions?
Hashimoto thyroiditis (aka chronic autoimmune thyroiditis).
89
What is Hashitoxicosis
Transient hyperthyroid state preceding Hashimoto thyroiditis due to follicular rupture and thyroid hormone release
90
What is the most common cause of hyperthyroidism? Tell me about it.
Graves disease.
Thyroid-stimulating immunoglobulin stimulates TSH receptors on thyroid --> diffuse goiter.
Also stimulates dermal fibroblasts (pretibial myxedema) and orbital fibroblasts (Graves orbitopathy).
Often presents during stress (e.g. pregnancy)
91
What is the most common type of thyroid cancer?
Papillary carcinoma.
Good prognosis.
On histology: orphan annie eyes, psamomma bodies
92
Tell me about medullary thyroid carcinoma
From parafollicular C cells.
Produces calcitonin
93
Labs (TSH, T4, T3) in primary hypothyroidism
Low TSH
Low T4
Normal T3
(T3 is converted peripherally and has low prognostic value)
94
Antibodies target what in Graves disease?
Thyrotropin (TSH) receptors
95
What is Zollinger-Ellison syndrome?
Endocrine disorder = mutation of the G cells in the **pancreas and duodenum**. Can be benign or malignant.
3 pathologies: gastrinoma (gastrin-secreting tumor) = increased gastric acid secretion from parietal cells = peptic ulcers
96
