Here are the explanations for questions on the endocrine quiz.
1. Acromegaly is a chronic metabolic disorder of adults caused by an overabundance of:
A. Parathyroid hormone
B. Growth hormone *
C. Epinephrine
D. Thyroid hormone
Easy one.
2. A 58-year-old female has had a 20-pound weight gain over the past two years. She has
noticed increasing cold intolerance and sluggishness. On physical exam her heart rate is
decreased, and her reflexes are delayed. Her serum TSH is 11.8 mU/L (normal = 0.3 - 3.0), and
her T4 is 2.3 micrograms/dL (normal = 4.5 - 12.5). A year ago, anti-TSH-receptor antibodies were
detected at high titer. Which of the following diseases does she most likely have?
A. Papillary thyroid carcinoma
B. Hashimoto thyroiditis *
C. Goiter
D. Graves disease
The symptoms this patient is having are consistent with hypothyroidism, and her T4 level
confirms this. It must be a case of primary hypothyroidism, since the TSH is elevated. Among the
choices give, only Hashimoto's leads to hypothyroidism.
A couple other clues to the diagnosis: the patient is female (not definitive, of course, but
Hashimoto's - like other autoimmune diseases - tends to happen more frequently in females),
and she has had elevated anti-TSH-receptor antibodies. Anti-TSH-receptor antibodies can be
seen in both Hashimoto's and Graves disease (weird; they do totallly opposite things in the two
diseases). There is another type of antibody called the anti-peroxidase antibody which is more
specific for Hashimoto's.
3. Extreme hypothyroidism in adults is called:
A. Addison disease
B. Graves disease
C. Myxedema *
D. Rickets
By the way, the term for severe congenital hypothyroidism is "cretinism", from the French Cretin,
or Christ-like. It was coined many many years ago, when these children were thought to be so
severely mentally retarded that they were incapable of sinning.
4. All of the following are true regarding type I diabetes EXCEPT:
A. It accounts for 90% of all cases of diabetes *
B. The body makes little or no insulin
C. Daily injections of insulin are required to sustain life
D. Long-term complications may include: hyaline arteriolosclerosis, proliferative retinopathy,
nodular glomerulosclerosis, and peripheral neuropathy
E. It is usually diagnosed in childhood or early adulthood
The point of the question is to remind you that type I diabetes (insulin-dependant, or juvenile,
diabetes) is much less common than type II diabetes (non-insulin dependant, or adult-onset,
diabetes). Type I is usually much more severe, too, with little or no insulin secretion at all.
Patients rely on insulin injections for their entire lives.
5. Addison disease is caused by damage to the:
A. Pancreatic islets
B. Thyroid gland
C. Parathyroid glands
D. Adrenal cortex *
Hopefully the case we look at in class will help you remember some things about Addison
disease.
6. Positive Chvostek and Trousseau signs indicate:
A. Botulism
B. Rickets
C. Tetany *
D. Bell's palsy
Tetany is a general name for a bunch of clinical symptoms related to hypocalcemia. These
include mild things, like muscle twitches and carpal spasm, and severe things, like laryngospasm
and seizures. Chvostek sign is elicited by tapping or stroking the facial nerve (above the
mandibular angle, adjacent to the earlobe); facial twitching or spasm results. Trousseau sign
occurs when you apply a blood pressure cuff to the patient's arm; carpopedal spasm results. I
remember which is which by remembering that to elicit Chvostek sign, you stroke the cheek.
7. A 55-year-old patient presents with recently diagnosed diabetes. He also has front teeth that
are more widely spaced than normal and have recently begun to flare. Which undiagnosed
disease does this patient most likely have?
A. Gigantism
B. Hyperparathyroidism
C. Paget's disease of bone
D. DiGeorge syndrome
E. Acromegaly *
Sometimes, in patients with acromegaly, the tongue gets so big that it pushes the anterior teeth
foward, so that they flare out. Another dental sign that may occur is wide spacing of the teeth
(as the jaw grows bigger and bigger).
8. A patient presents with osteomalacia, loss of the lamina dura around the teeth, brown tumors
in bone, and duodenal ulcers. His family reports his personality has changed. Which of the
following disorders should you suspect him of having?
A. Hyperparathyroidism
B. Hypoparathyroidism
Dr. Koutlas will talk about the "stone (kidney stones), bone (brown tumors), groan (GI
symptoms) and moan (mental changes)" symptoms in hyperparathyroidism. When you have too
much PTH around, your serum calcium goes down. Osteoclasts chew up bone at a greater rate,
leading to lamina dura loss, demineralization of alveolar bone, and - if severe enough - brown
tumors. These are not tumors at all, but just areas of bone that have cystic degeneration and
hemorrhage - hence the brown color - to such an extent that it shows up as a tumor-like mass
on x-ray.
9. All of the following statements regarding multiple endocrine neoplasia II are true EXCEPT:
A. Patients have increased incidence of thyroid carcinoma
B. Patients have increased incidence of pheochromocytoma
C. Patients have increased incidence of mucosal neuromas
D. It is autosomal recessive *
E. Differential diagnosis includes von Recklinghausen's disease
The Multiple Endocrine Neoplasia (MEN) syndromes are genetic syndromes that predispose
patients to developing endocrine tumors. Endocrine tumors occuring in patients with MEN
syndromes tend to be more aggressive and occur at younger ages than their sporadic
counterparts (i.e., the prognosis of medullary carcinoma of the thyroid is pretty bad when it
occurs sporadically, but when it occurs in the context of MEN, it happens at a younger age and
has an even worse prognosis).
There are two main kinds of MEN syndromes (MEN 1 and MEN 2); MEN 2 is further split into 2a
and 2b. While both types 1 and 2 increase the patient's risk of developing multiple endocrine
tumors (hence the "MEN" name), there are some differences in the specific kinds of endocrine
tumors commonly seen in each syndrome.
In class, we will boil it down to the simplest possible terms. The big thing about MEN 2 is that
patients have a markedly increased risk of developing medullary carcinoma of the thyroid. These
patients can get other things too (like pheochromocytoma, and occasionally parathyroid
hyperplasia), but the thing that virtually all patients end up getting is medullary carcinoma of the
thyroid.
Patients with MEN 1 don't have an increased risk of medullary carcinoma of the thyroid - but
they do have an increased risk of a whole bunch of other things, including parathyroid
hyperplasia, pancreatic carcinoma, and pituitary adenoma (the three Ps).
So, to simplify it to a ridiculous degree: MEN 2 = medullary thyroid carcinoma. MEN 1 =
everything else.
It's more complicated than that, of course. One of the details that this question addresses is the
division of MEN 2 into two subtypes. MEN 2a is as described above (medullary thyroid
carcinoma in virtually all patients, sometimes pheochromocytoma, and occasionally parathyroid
hyperplasia). MEN 2b is like MEN 2a, except (1) patients usually do not develop parathyroid
hyperplasia, and (2) they often have other unusual findings, like neuromas (benign tumors of
nerves) or a Marfanoid habitus (very tall, with long fingers, arms, and legs).
Okay, so back to the question. A is true. B is true (not everyone gets this, like medullary thyroid
carcinoma, but the incidence is increased). C is true in MEN 2b. D is not true.
In MEN 1, the genetic mutation is in the MEN gene, which is a regular old tumor-suppressor
gene. A tumor suppressor gene puts brakes on cell growth, and if you get a genetic mutation
that inactivates the gene, the brakes will come off and the cell will grow like crazy. Like any
tumor suppressor gene, you have to lose both alleles to get disease (so you'd call it autosomal
recessive). It's your basic run-of-the-mill old tumor suppressor gene, just like old run-of-the mill
Brad Pitt. You have to inactivate the gene to get tumors, just like big old inactive Brad Pitt. (Sorry
Brad, but we need an analogy and you’re it.)
In MEN 2, the genetic mutation is in the RET gene, which is a proto-oncogene. An oncogene is a
normal gene that encodes something that makes a cell grow (like a growth receptor or
something). If you mutate an oncogene in such a way that it has a gain of function (meaning it's
always turned on), then it becomes a proto-oncogene, and you get uncontrolled cell growth.
You only need to mutate one copy of a proto-oncogene to get malignancy (unlike tumor
suppressor genes), so you'd call MEN 2 autosomal dominant. This is unusual! Most genetic
syndromes that predispose people to getting cancers have abnormalities in tumor suppressor
genes, not proto-oncogenes! So - the genetic abnormality in this syndrome is very unique (just
like John Cleese, who is truly one-of-a-kind). And not only that, but the gene is always turned on
in this syndrome (just like John Cleese - at least when he's holding my picture. This will make
sense after class).
Whew.
Finally, E is true. Wait a minute, you're saying - didn't you say von Recklinghausen's disease was
that disease with all the brown tumors? Osteitis fibrosa cystica? Yes, I did say that. It just so
happens that there are TWO von Recklinghausen's diseases. How crazy is that? One von
Recklinghausen's disease is caused by hyperparathyroidism and manifests with brown tumors.
It's also called osteitis fibrosa cystica. The other von Recklinghausen's disease is a hereditary
disorder that manifests with multiple, diffuse neurofibromas (a benign tumor of nerves) and
many other abnormalities. It is one of two diseases called neurofibromatoses. Wikipedia has
good articles about the bone-related von Recklinghausen's disease, the neurofibromatosis type
of von Recklinghausen's disease, neurofibromatosis in general (types 1 and 2), von
Recklinhhausen himself, and the elephant man (who was thought until recently to have suffered
from the neurofibromatosis form of von Recklinghausen's disease).
10. Which of the following symptoms would be most likely in a patient with
pheochromocytoma?
A. Headache *
B. Hypotension
C. Bradycardia
D. Dry skin
E. Hypoglycemia
Pheochromocytoma is a tumor of the catecholamine-producing cells of the adrenal medulla. The
catecholamines (epinephrine and norepinephrine) do a bunch of things; they are the "flight or
fight" hormones that get released under severe stress. One of the main things they do is
increase blood pressure - so that's why people with pheochromocytoma can present with
hypertension. Because the catecholamines may be released in waves, the hypertension may be
paroxysmal. And because it doesn't respond well to normal blood pressure medications, it can
be termed persistent. Other things catecholamines do in real life (not so much in this tumor,
though) are: increase the basal metabolic rate and raise the blood glucose level.
By the way, neuroblastoma is another tumor we will talk about in the context of adrenal
medulla. It's a tumor of neural crest cells, and it's the most common malignant tumor of
childhood. It can sometimes secrete hormones (weird - it's composed of neural-type cells, not
hormone-producing cells - but tumors can do whatever they want) including catecholamines,
which can result in increased heart rate and blood pressure. Most neuroblastomas, however,
present with an abdominal mass (or a sense of fullness or pain in the abdomen), not with
hypertension or tachycardia.
Back to the question. Pheochromocytoma can present with a lot of different symptoms, the
most common of which is hypertension. If you want another mnemonic (who doesn't?),
remember the 6 Hs (all of which are related to high catecholamine levels):
Hypertension
Headache
Hyperhidrosis (sweating)
Heart palpitations
(tachycardia)
Hypermetabolism
Hyperglycemia
11. Cushing Syndrome may be caused by all of the following EXCEPT:
A. An adrenal cortex tumor
B. A posterior pituitary tumor
*
C. A paraneoplastic syndrome
D. Iatrogenic factors
Sneaky - Cushing Syndrome may be caused by an anterior pituitary tumor, not a posterior one.
12. Patients with Graves Disease may show all of the following EXCEPT:
A. Decreased appetite *
B. Exophthalmos
C. Heat intolerance
D. Tachycardia
E. Irritability
Patients with Graves Disease show some or all the symptoms of hyperthyroidism (including
tachycardia, heat intolerance, sweating, weight loss, diarrhea, mental changes, etc.). Many
patients also show exophthalmos, and a few have a dermopathy.
13. Which of the following is associated with Addison disease?
A. Central obesity
B. Diabetes
C. Osteoporosis
D. Hypotension *
E. Increased appetite
Patients with Addison disease have little or no aldosterone and cortisol secretion. Therefore,
there are problems with blood pressure and salt regulation (patients get hyponatremic and
hypotensive, and crave salty foods), and problems related to the low cortisol level (like
hypoglycemia and a decreased immune response to infections). Remember that patients with
Addison disease will also show hyperpigmentation because the pituitary responds to the low
glucocorticoid levels in the blood by making more ACTH, and ACTH comes from a larger
precursor molecule that gives rise to melanocyte-stimulating hormone! The hyperpigmentation
may manifest as diffuse skin bronzing, or it may show up in focal areas, like skin folds, or in the
mouth, as seen in this patient:
14. Patients with hypothyroidism may show all of the following symptoms EXCEPT:
A. Short stature
B. Retention of deciduous teeth
C. Stunted skeletal growth
D. Hair in the oral cavity *
E. Mental slowness
Eww. If anything, hair growth would slow down. Everything slows down in hypothyroidism.
15. Which of the following is a function of the parathyroid glands:
A. Secrete calcitonin
B. Decrease serum calcium
C. Stimulate osteoclasts *
D. Increase renal reabsorption of phosphate
Easy one.