Download Who wants to be an Endocrine Millionaire?

10/7/2009
Overview
Current
Trivia
Clinical Scenarios
Who wants to be an
Endocrine
Millionaire?
S. Sethu K. Reddy, MD, MBA
1
Who wants to be an Endocrine
Millionaire?
1
5
9
13
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6
10
14
3
7
11
15
4_
8
12
16
10/7/2009
2
This gentleman
should be most
worried about:
A.
B.
C.
D.
Hands
Joints
Heart
Liver
10/7/2009
3
Image depicts:
A.
B.
C.
D.
E.
2-month fetus
Left thyroid cyst
Right thyroid
echogenic solid
nodule
Thyroid cyst
Full bladder
10/7/2009
4
19 y.o.
female with
sarcoidosis
and a
sodium of
154 mEq/l
A.
B.
C.
D.
Empty sella
Pituitary adenoma
Absent stalk
Micronodular leptomeningeal
enhancement
10/7/2009
Argyropoulou, Maria I. Kiortsis, Dimitrios Nikiforos.
Pediatric Radiology; 2005-11-01
Caption/Legend:
A 19-year-old-girl with sarcoidosis and central diabetes insipidus. a Midsagittal,
unenhanced T1-W MRI shows thickening of the superior half of the pituitary stalk and
absence of the posterior pituitary lobe high signal. b Midsagittal contrast enhanced T1weighted shows enhancement of the pituitary stalk-pituitary gland complex and
micronodular leptomeningeal enhancement The MRI shows lack of the posterior lobe bright
signal and thickening of the pituitary stalk (Fig. 13 ).
Title: MRI of the hypothalamic-pituitary axis in children
Publisher: Springer
Authors:
Argyropoulou, Maria I.
Kiortsis, Dimitrios Nikiforos
Journal title: Pediatric Radiology
DOI: 10.1007/s00247-005-1512-9
Published Date: 2005-11-01
5
Posterior Pituitary
10/7/2009
Absence of the normal posterior pituitary bright spot should prompt a search for an
ectopic posterior pituitary that has failed to migrate inferiorly from the
hypothalamus
6
This person with diabetes and
numbness with loss of proprioception
with normal pain sensation likely
has:
A.
B.
C.
D.
Large fiber neuropathy
Carpal tunnel
syndrome
Small fiber neuropathy
causing small muscle
wasting
Associated with
painful symptoms
Authors: Vinik, Aaron, Skyler, Jay
Atlas of Clinical Endocrinology; 2002
10/7/2009
Caption/Legend:
Large fiber neuropathy in diabetes Figure 15-4. Wasting of the small muscle of the hand
in large fiber neuropathies. This must not be mistaken for ulnar entrapment, which is
amenable to treatment. In large fiber neuropathies all peripheral nerves are affected equally
and the sensory disturbance is of the “glove and stocking” variety not confined to the nerve
distribution. In ulnar entrapment the sensory loss involves the ring and little fingers.
Title: Diabetic Neuropathies
Publisher: ImagesMD
Authors:
Vinik, Aaron
Skyler, Jay
Book title: Atlas of Clinical Endocrinology
Published Date: 2002-01-28
7
Although CT imaging of adrenals
is preferred, when is MRI more
useful?
A.
B.
C.
D.
E.
Conn
Adrenal Cushing
Pheochromocytoma
CMV infection of adrenals
Children with adrenal lesions
10/7/2009
Currently, the adrenal glands can be readily imaged by CT, sonography, and magnetic resonance imaging (MRI) [], []. Hence,
invasive procedures such as arteriography, venography, or venous sampling are now seldom required for diagnosis. CT
scanning is the most valuable imaging technique []. The abundant perinephric fat present in most patients allows the clear
display of the adrenal glands. Tumors as small as 10 mm are routinely identified using contiguous 5–mm collimated slices.
The adenomas of Conn’s syndrome (hyperaldosteronism) are the most difficult lesions to detect on CT because they are the
smallest lesions, usually measuring less than 2 cm in diameter []. Adrenal venous sampling can be helpful in patients with
Conn’s syndrome because of the small size of the tumor as well as the presence of bilateral disease [].
In contrast, venous drainage studies are rarely needed in patients with adrenal Cushing’s syndrome because of the larger size of
the lesions and the abundant retroperitoneal fat. MRI does not provide additional useful information in most patients with
Cushing’s or Conn’s syndrome [], [].
Sonography may be useful to study the retroperitoneum in children because of the paucity of fat.
Although the spatial resolution of MRI is inferior to CT, the intense T2–weighted signal demonstrated by most
pheochromocytomas makes MRI useful in differentiating these tumors from cortical adenomas []. Moreover, MRI may help to
demonstrate extra–adrenal pheochromocytomas (urinary bladder and paracardiac region) []. Although 131I meta–iodobenzyl
guanidine (MIBG) scanning seems to be similar in overall accuracy to CT and MR for localization of pheochromocytoma, it is
only occasionally used for whole body imaging to detect ectopic tumors or metastatic deposits []. Most nonfunctional adrenal
masses are incidentally detected on abdominal CT examinations performed for another purpose.
8
Which presidential family likely
had HLA DR-3 DQ2 or DR-4DQ8 haplotypes?
A.
B.
C.
D.
E.
Adams
Lincoln
Roosevelt
Kennedy
Bush
Mandel L. Annals Int Med 2009; 151:350-354
10/7/2009
JFK is now known to have Addison’s, plus hypothyroidism, pernicious anemia.
Sister Eunice was known to have Addison’s and JFK Jr. was known to have
Graves’.
The spectrum suggests APS-2 (auto-immune polyglandular syndrome), related to
HLA DR-3 DQ2 and HLA DR-4-DQ8 halplotypes. This is not related to APS-1
which often begin sin infancy and is linked to the AIRE gene.
9
CT Abd: patient with FUO
and hypoadrenalism
A.
B.
C.
D.
10/7/2009
Adrenal TB
Histoplasmosis
Lymphoma
Bilateral
adrenal
hemhorrage
Mantzios G. et al
Annals of Hematology
2004-07-01
CT scan of the abdomen: bilateral enlargement of adrenal glands Computed
tomography (CT) scanning of the thorax did not reveal any abnormal finding, while CT
scanning of the abdomen disclosed bilateral adrenal gland enlargement (right adrenal
diameters 9×3cm, left adrenal diameters 10×3.5 cm) (Fig. 1 ). .
Title: Primary adrenal lymphoma presenting as Addison’s disease: case report and review
of the literature
Publisher: Springer
Authors:
Mantzios, George
Tsirigotis, Panagiotis
Veliou, Filio
Boutsikakis, Iosif
Petraki, Lillian
Kolovos, John
Papageorgiou, Sotirios
Robos, Yannis
Journal title: Annals of Hematology
Published Date: 2004-07-01
10
A 2-month-old
male with
Unenhanced CT
image with
bilateral adrenal
calcification
A.
B.
C.
D.
Neonatal TB
Severe hyperparathyroidism
Adrenoleukodystrophy
Wolman disease
10/7/2009
Caption/Legend:
A 2-month-old male with Wolman’s disease. Unenhanced CT image demonstrates an
enlarged liver and bilateral adrenal calcification (arrows), which conforms to the normal
shape of the adrenal glands. (Case courtesy of John Doppman, MD) The adrenal glands are
enlarged and contain calcifications, but maintain their normal shape (Fig. 5 ). .
Title: Adrenal gland and adrenal mass calcification
Publisher: Springer
Authors:
Hindman, Nicole
Israel, Gary M.
Journal title: European Radiology
DOI: 10.1007/s00330-004-2509-8
Published Date: 2005-06-01
Acid lipase deficiency in family of lysosomal storagae disorders .
++++ cholesteryl esters and TG accumulation
11
A 26 y.o. male presents with a history of episodic
hypertension and a left adrenal mass and a smaller
tumor in the hilus of the liver. Thought to be a
metastasis but no mention of lymphatic tissue in the
pathology. Family history was negative. Found to be
negative for mutations in VHL or RET genes.
Subsequently, he was found to have a germline
mutation in SDH (succinate dehydrogenase) gene. He is
now asymptomatic and urine screening is negative.
Which diagnostic test would confirm your diagnosis?
A.
B.
C.
D.
MIBG scan of Abdomen
MRI of Chest
MRI of brain
MRI of Neck
Neumann and Eng JCEM 94: 2677-2683, 2009
10/7/2009
12
10/7/2009
Paraganglial tumors in the reported case. A, Abdominal CT before the first operation with left
adrenal pheochromocytoma. B, Abdominal CT before the second operation with extraadrenal
pheochromocytoma and complete infarction of the left kidney. C, Pheochromocytoma of the right
adrenal gland, detected 4 yr after first surgery. D, Left carotid body tumor operated 8 yr after first
surgery.
Red flags for genetic cause: younger age of onset (Sporadic cases occur on one’s 40s typically).
The paraganglioma syndromes (PGL) have been classified by genetic analyses of families with
HNPs. Numbering the syndromes type 1 to type 4 follows publication dates of the reports (17, 18, 19,
20). Three of the four PGL predisposition genes have been identified, namely, SDHB, SDHC, and
SDHD (21). The susceptibility genes encode three of the four subunits of the enzyme succinate
dehydrogenase (SDH) or mitochondrial complex II, which lies at the pivotal juncture of the
respiratory (electron transport) chain and the Krebs cycle (21). Complex II comprises two structural
units, which anchor the enzyme (catalytic sites encoded by A and B subunits) to the mitochondrial
membrane (subunits C and D). SDHB, located on 1p36, consists of eight exons and is the
predisposition gene for PGL 4, SDHC (located on 1q36, 6 exons) for PGL 3, and SDHD (located on
11q23, 4 exons) to PGL 1 (Table 1 ). The gene for PGL 2, mapped to 11q13, has not yet been
identified. Mutations of SDHA do not predispose to development of paraganglioma tumors but
homozygous or compound heterozygous mutations cause Leigh syndrome. The most prevalent
among these syndromes is PGL 1, caused by germline SDHD mutations, followed by PGL 4
(SDHB), whereas PGL 3 (SDHC) is rare. The spectrum of manifestations of PGL 1, PGL 3, and PGL
4 shows differences but also overlap. Adrenal, extraadrenal abdominal, and thoracic
pheochromocytomas are components of PGL 1 and PGL 4 but very rarely of PGL 3 (6, 7, 22, 23, 24,
25). Patients with PGL 1 (SDHD mutation carriers) nearly always display benign and multiple
adrenal pheochromocytomas and HNPs (7, 22). Patients with PGL 4 (SDHB mutation carriers) often
display extraadrenal or thoracic or HNPs (7, 22). About one third of the patients have metastases.
Patients with PGL 3 (SDHC mutation carriers) have characteristics of age, manifestation, and tumor
number similar to those with sporadic HNPs (23).
13
Visual Vignette
40 y.o. woman with a vascular sub-glottic
mass staining for neuron-specific enolase,
chromogranin and synaptophysin
Leung S, Storck K, Le Francois Endocrine Practice 15:175; 2009
10/7/2009
14
A.
B.
C.
D.
E.
40 y.o. man with hx of craniopharyngioma
was treated with GH from age 1973 to
1985. Has now developed forgetfulness,
ataxia, prominent cerebellar sx. EEG
showed genera slow-wave activity. Likely
diagnosis:
Spread of craniopharyngioma
Nutritional encephalopathy
Dementia praecox
Creutzfeldt-Jakob Disease
Jakob-Creutzfeldt Disease
Dixit K et al. JCEM 94:2684-2685; 2009
10/7/2009
Iatrogenic Creutzfeldt-Jakob Disease: preogressive cerebellar syndrome, often
involving basal ganglia, caudate nucleus
MRI features: high signal in fluid-=attenuated inversion recovery and diffusion
weighted imaging in caudate nucleus
First reported in 1985.162 cases have been reported: France, UK and USA
primarily.
Incubation period could be several decades.
15
Which of these statements is
FALSE re. perchlorate?
A.
B.
C.
D.
Perchlorate is a potent stimulator of the
sodium-iodide symporter.
Has been used to treat Graves and iodine
induced hyperthyroidism.
Perchlorate salts have been used as
oxidizers in missiles and rockets.
Chilean wine may harbor perchlorates.
Braverman L. Endo Practice 15: 50-54; 2009
10/7/2009
Perchlorate is a competitive inhbitor of NIS. Inhibitors include perchlorate,
thiocyanate and nitrate in order of potency.
Recent epi- studies suggest that almost everyone in the US has perchlorate in their
urine. It Is not clear whether perchlorate in drinking water has any link to thyroid
disorders.
16
Which of these MRI patterns (T1 and T1 with
contrast) is most consistent with hypophysitis?
A) Hyperintense and no change with contrast
B) Hypointense and enhance with contrast
C) Isointense and enhance with contrast
D) Hypointense and hypointense with contrast
10/7/2009
17
MRI of Sellar Masses
T1 Images and T1 with Contrast
Hyperintense and no change with contrast
– craniopharyngioma, Rathke’s cleft cyst
Hypointense and enhance with contrast
– Hypophysitis
Isointense and enhance with contrast
– Meningioma, metastasis, glioma
Hypointense and hypointense with contrast
– Pituitary adenoma
10/7/2009
18
Craniopharyngioma
10/7/2009
19
Hyperintense post-contrast enlargement (Hypophysitis)
10/7/2009
20
10/7/2009
Figure 1 The patient's preoperative and postoperative pituitary MRI scans
Nachtigall LB (2006) Acromegaly diagnosed in a young woman presenting with headache and arthritis
Nat Clin Pract Endocrino Metabol 2: 582–587 doi:10.1038/ncpendmet0301
21
Paget disease of bone: Which
statement is FALSE?
A.
B.
C.
D.
A normal Alkaline Phosphatase rules out
Paget disease.
Has been reported to be associated with
hydrocephalus, dementia and intracranial
hemorrhage.
The optic nerve could be affected.
The risk of Paget disease in first-degree
relatives of affected individuals is 10 fold.
Rubin D, Levin R. Endo Practice 15: 158-166; 2009
10/7/2009
86% of pats with PDB may have normal alk phos.
22
Which of these statements is
TRUE regarding flushing
disorders?
A.
B.
C.
D.
Carcinoid syndrome can result in pellagra
due to tryptophan depletion.
Nicotinamide is associated with acute
facial flushing.
Flushing with mastocytosis is associated
with calcitonin and substance P.
Sulfonylurea associated alcohol-induced
flushing occurs in nearly all.
10/7/2009
Nicotinamide does not cause flushing..
Niacin (nicotinic acid) causes flushing.
Mastocytosis flushing has been linked to histamine, PGD2, leukotrienes. DX: serum
tryptase or urine methyl-histamine.
Medullary Cancer has been associated calcitonin and Substance P.
The SFU associatedEtOH induce flush is thought be an inherited trait.
23
Which of these is not a predictor for
successful remission (app. 12
months) after discontinuation of
dopamine agonist therapy for
prolactinomas?
A.
B.
C.
D.
E.
Having been treated for at least 2 years with a
low normal PRL level
Shrinkage of tumor by at least 50%
Those with non-tumoral hyperprolactinemia
To be at least 5 mm away from optic chiasm
No invasion of cavernous sinus
Kharlip J , Salvatori R, et al. JCEM, 94:2428-2436; 2009
10/7/2009
Caveats:
Even with these predictors, only 50% are still in remission after 12 months.
The interest is based on reports of heart valve abnorrmailties with chronic high-dose
DA Rx for Parkinson’s.
Important need for periodic monitoring.
24
Which of the following has been
cited as a biological reason for
some patients to feel the
psychological benefit of T3
therapy addition?
A.
B.
C.
D.
De-iodinase gene variant
TBG gene variant
Ability of T3 to cross blood-brain barrier
Mutations in TR- 2 (homologous to c-erb-A)
Panicker V, et al. JCEM 94:1623-1629; 2009
10/7/2009
Despite one NEJM study showing the benefit of T4-T3 therapy, 10 subsequent studies have failed to
demosntrate a benefit.
The rarer CC genotype of the rs225014 polymorphism in the deiodinase 2 gene (DIO2) was present
in 16% of the study population and was associated with worse baseline GHQ scores in patients on T4
(CC vs. TT genotype: 14.1 vs. 12.8, P = 0.03). In addition, this genotype showed greater
improvement on T4/T3 therapy compared with T4 only by 2.3 GHQ points at 3 months and 1.4 at 12
months (P = 0.03 for repeated measures ANOVA). This polymorphism had no impact on circulating
thyroid hormone levels.
We used genotype data from the Caucasian European individuals in the International Haplotype
Mapping Project (http://www.hapmap.org) to select a set of SNPs that capture the majority of
common variation across the three deiodinase genes (DIO1, DIO2, and DIO3) including 50 kb either
side of the genes. We used a minor allele frequency of at least 10%. The 21, seven, and seven SNPs
in the DIO1, DIO2, and DIO3 genes required nine, four, and six SNPs, respectively, to capture all
common variants with an r2 > 0.8. These were: D1, rs11206237, rs11206244, rs2235544, rs2268181,
rs2294511, rs2294512, rs4926616, rs731828, and rs7527713; D2, rs12885300, rs225011, rs225014,
and rs225015; and D3, rs1190716, rs17716499, rs7150269, rs8011440, rs945006, and rs1190715.
We used only SNPs that were in Hardy Weinberg equilibrium (P > 0.05) and were genotyped in at
least 97.5% of the samples in the final analyses. We examined the association between these SNPs
and baseline (before randomisation) psychological well-being.
There are three forms of the thyroid hormone receptor designated alpha-1, beta-1 and beta-2 that are
able to bind thyroid hormone. There are two TR-alpha receptor splice variants encoded by the THRA
gene and two TR-beta isoform splice variants encoded by the THRB gene:[2]
TR-α1 (widely expressed and especially high expression in cardiac and skeletal muscles)
TR-α2 (homologous with viral oncogen c-erb-A, also widely expressed but unable to bind hormone)
TR-β1 (predominately expressed in brain, liver and kidney)
TR-β2 (expression primarily limited to the hypothalamus and pituitary)
25
HIV associated lipodystrophy:
Which statement is FALSE?
A.
B.
C.
D.
Related to highly active
anti-retroviral therapy
Fat wasting is more
common in younger
females
Circumscribed lipomas
have also been observed.
Increased TG, LDL-C
and reduced HDL-C are
typically observed in this
syndrome.
Virusmyth.com 10/7/2009
and dermatalogy.cdlib.org; JCEM 2008;93:2937-2945 T. Brown
There are multiple risk factors for the development of lipoatrophy. Fat wasting is more common in males, older patients, and those who
started HAART with advanced HIV (7, 8, 10). Although lipoatrophy was initially recognized after the introduction of PIs (3), most
evidence suggests that the medications most closely tied to its development are the nucleoside reverse transcriptase inhibitors (NRTIs),
stavudine (Zerit, d4T; Bristol-Myers Squibb Co., Princeton, NJ) and, to a lesser extent, zidovudine (Retrovir, AZT; GlaxoSmithKline,
Research Triangle Park, NC) (15). These medications inhibit the synthesis of mitochondrial DNA preferentially in adipocytes, leading to
mitochondrial dysfunction and adipocyte apoptosis (16). Some members of the PI class, such as nelfinavir, can act synergistically with
stavudine to worsen lipoatrophy (4). A recent large clinical trial showed unexpected worsening of lipoatrophy in HIV-infected patients
randomized to the non-NRTI, efavirenz, but the mechanism underlying this observation is not clear (17). This patient developed fat
wasting in the first 12–24 months after initiation of the stavudine-containing HAART regimen. Although he has since changed to other
antiretroviral medications, he has not experienced significant recovery of his sc fat. In the assessment of HIV-infected patients with body
composition changes, it is useful to have objective measures of body composition to be able to gauge longitudinal changes. I typically
measure the waist at the iliac crest, the hip around the greater trochanter, and thigh at a fixed distance from the top of the patella. In select
patients who continue to receive stavudine or zidovudine and who have minimal or no lipoatrophy on physical examination, whole body
dual x-ray absorptiometry can be a useful tool to document subclinical worsening of lipoatrophy, which may be an important factor in the
consideration of modifying the antiretroviral regimen. Previous photographs can be useful for the assessment of facial lipoatrophy, and
grading scales have been developed based on abnormalities in facial contour, prominence of bony structures, and visibility of the
underlying musculature (13, 18, 19).
In addition to lipoatrophy, this patient also presented with abdominal and dorsocervical fat accumulation. In other patients, circumscribed
lipoma in other areas of the body (e.g. suprapubic) and lipomastia in both men and women can also be observed. Unlike lipoatrophy, the
pathogenesis of lipohypertrophy among HIV-infected patients has been elusive and cannot be linked to a specific antiretroviral medication
or class of medications. With the initiation of antiretroviral therapy, most studies have shown an increase in central fat over the first 6
months, which then levels off (4, 20). Some of this increase may be due to a return to premorbid body composition with effective control
of the HIV virus and "catch-up" to HIV-negative peers. However, visceral fat in HIV-infected patients with lipodystrophy exceeds that
observed in HIV-negative controls when matched on BMI (21).
The assessment of HIV-lipohypertrophy can be difficult in practice, and there is no commonly accepted definition. Because central fat
accumulation is common in the general population, it can be challenging to ascertain the contribution of the fat gain that is specific to HIV
infection or its therapy. In addition, because some patients have a combination of sc lipoatrophy in the abdominal region and visceral
lipohypertrophy, clinical measurements of central adiposity that do not distinguish between sc and visceral fat, such as waist
circumference, may be misleading. For example, a waist circumference that is considered normal in the general population may indicate a
significant amount of visceral fat in a HIV-infected patient with concomitant sc lipoatrophy.
Previously, it was believed that lipoatrophy and lipohypertrophy were reciprocal processes, whereby the loss of sc fat was associated with
gains in the visceral compartment. This notion was challenged when it was found that those HIV-infected patients with clinical lipoatrophy
were found to have either equal or less visceral fat compared with those HIV-infected patients without lipoatrophy, arguing against a strict
"fat redistribution syndrome" (5, 6).
Dyslipidemia, characterized by increased LDL cholesterol and TGs, and decreased HDL cholesterol, is common among HIV-infected
patients receiving HAART (22). Before the HAART era, decreased HDL, LDL, and total cholesterol, accompanied by decrease TG
clearance were recognized among HIV-infected patients (23). As was seen in this patient, initiation of antiretroviral therapy can be
associated with dramatic changes in lipid concentrations, particularly TGs, although HDL and LDL also increase but to a lesser extent (24).
In vitro studies have shown that certain PIs increase TG synthesis (25), and there is variability among the clinical effect of individual
agents within the PI class (24). However, it should be noted that individual PIs are often given in combination low doses of ritonavir, a PI
that inhibits cytochrome P450 3A4, which is the primary metabolic pathway of PIs. Coadministration with ritonavir increases PI serum
concentrations and improves the pharmacokinetic profile. Although not active against HIV at these "boosting" doses, ritonavir may also
worsen dyslipidemia (26). Other antiretroviral medications may contribute to dyslipidemia, including efavirenz, stavudine, and zidovudine
(27, 28, 29). In addition, recent evidence suggests that both increases in visceral fat and reductions in lower body sc fat are independently
associated with dyslipidemia in both HIV-infected men and women (30, 31).
26
Supplemental Questions
From the Past
10/7/2009
27
Which of these statements is TRUE
about osteonecrosis of the jaw?
A) Usually occurs spontaneously
B) Characterized by localized jaw pain and
exposed necrotic bone
C) More cases have been reported with
bisphosphonate use with osteoporosis than with
myeloma or solid malignant tumors.
D) Discontinuing bisphosphonate therapy before
an oral surgical procedure has been shown to
reduce the incidence of ONJ.
JCEM 2007;92:817-818
10/7/2009
Often follows trauma or surgery. Only 4-5% of ONJ cases have been in patients
taking bisphosphonates for osteoporosis. There is no proof that stopping the oral
bisphosphonate before an oral surgical procedure.
28
Post-TBI is becoming a more
common event. Which of these is
TRUE?
A) Associated with fatigue and irritability but not
loss of memory or concentration ability.
B) With fatal head injury, only 25% are found to
have some form of pituitary injury.
C) 5% of boxers were found to be GH deficient.
D) In the chronic Post-traumatic brain injury
scenario, 25-50% have been found to have an
element of hypopituitarism..)
10/7/2009
All of these symptoms in choice A can occur with TBI.
75% were found to have pititary injusry with fatal head injury.
45% of boxers were found to be GH deficient.
(GH deficiency and GnRH deficiency are most common in the hypopituitarism.
29
Which of these is NOT an effect
of obesity on testicular function?
A.
B.
C.
D.
Increases aromatization of testosterone
Sleep apnea may induce testicular
dysfunction.
Diminishes semen quality
Increases SHBG
10/7/2009
Obesity
Increased aromatization of T to Estradiol which can then inhibit HPG axis.
Sleep apnea induces central hypogonadism
Leptin resistance and elevated leptin levels may inhibit androgen synthesis
Diminishes semen quality
Obesity decreased SHBG.
30
Which of these statements re.
familial hyperaldosternism is
FALSE?
A.
B.
C.
D.
Primary aldosteronism is the most frequent form
of secondary hypertension.
Patients with hyperaldosteronism have the same
risk of stroke, MI and A. Fib. As essential
hypertensives.
There are now three forms of familial
hyperaldosteronism. (FH-I, FH-II, FH-III)
GRA is FH-I. (Autosomal dominant, elecated
ACTH-dependent aldo secretion, increased 18OH cortisol and 18-oxo-cortisol. Hypokalemia is
uncommon.)
10/7/2009
FH-1/GRA: genetic recombination between CYP11B-1 (11-beta hydroxylase) and
CYP11B-2 (aldosterone synthase), generating a chimeric enzyme. Most affected individuals
develop severe hypertension early in life with high likelihood of CVA.
FH-II is non-glucocorticoid remediable. Could be wither adrenal adenoma or hyperplasia.
This form is indistinguishable from sporadic PA. The genetic backgrond is still unkonown.
FH-III, recently described by Geller et al from Yale in JCEM 93:3117-3123, 2008:
characterized by severe hypertension in early childhood, withmarked hyperaldosteronism
and hypokalemia with significant end-organ damage. Patients were resistant to aldactone or
amiloride. The only cure was bilateral adrenalectomy. There is also enormous productino of
18-OH-F and 18-oxoF.
Sporadic PA: 18-OH-F and 18-oxoF are 3-4 times higher
FH-I: 10 times higher
FH-II: 3-4 times higher
FH-III: 10-1000 times higher.; also, DST actually led to paradoxical rise in aldosterone (2
X)
31
Which statement is most likely
incorrect re. Vitamin D?
A.
B.
C.
D.
Cholecalciferol is more potent than
ergocalciferol in increasing 25-OH-D levels.
Hypovitaminosis D can be associated with
muscle weakness and tendency to fall as well as
increased bone turnover.
Vit. D insufficiency has been also associated
with cancer, CVD, diabetes and increased
mortality.
25-OH vitamin D does not directly regulate PTH
levels.
10/7/2009
JCEM 2008;93:3015-3020; Romagnoli et al, Rome, Italy
Cholecalciferol is almost twice as potent than ergocaliferol, both po and im.
Raising 25-OH D levels can reduce bone turnover rate and suppress PTH levels.
The suppression may take at least 60 days.
32
Patient with these findings: What
would you warn the patient
about?
A.
B.
C.
D.
Peripheral vascular
disease
Optic neuritis
Abdominal pain
Diabetes Insipidus
10/7/2009
Eruptive xanthomas are yellow-orange-to-red-brown papules that are often surrounded by
an erythematous halo. They appear in crops on the buttocks, extensor surfaces of the
extremities, and flexural creases. Acutely, variable amounts of pruritus and pain occur. A
Koebner reaction may be present. Lesions usually resolve spontaneously over weeks and
may result in hypertrophic scars. Histologically, foamy macrophages are present in the
dermis with an inflammatory infiltrate of lymphocytes and neutrophils.
Eruptive xanthomas occur in the setting of chylomicronemia and hypertriglyceridemia. This
may be due to a primary hyperlipoproteinemia resulting from a genetic deficiency of
lipoprotein lipase (Type 1 hyperlipoproteinemia) or familial hyperlipoproteinemia (Type
V). Eruptive xanthomas often also occur secondarily in individuals unresponsive to insulin.
Insulin is required for the normal triglyceride clearing function of lipoprotein lipase.
Whenever insulin deficiency is present, an acquired liproprotein lipase deficiency exists,
which results in impaired clearance of chylomicrons and very-low-density lipoproteins
causing the resultant hypertriglyceridemia. Rarely, eruptive xanthomas have been reported
with hypothyroidism, nephrotic syndrome, and von Gierke's glycogen storage disease. They
have been noted also after ingestion of alcohol, glucocorticoids, estrogens, and retinoids.
33
Which of these has NOT been
associated with weight gain?
A.
B.
C.
D.
E.
Fused toe gene
Leptin receptor mutations
Belonging to a social network with friends
becoming obese
Reduced GLP-1 action
Altered intestinal flora
J. Clin Endocrinol & Metab Vol. 93, No. 6 2027-2034
10/7/2009
The most compelling recent data of genetic linkage comes from the FTO (fused toe gene in the mice) now re-titled (fat
mass and obesity-associated) gene. A number of variant alleles in the first intron of FTO have been shown in several
independent genome-wide association studies to be strongly and significantly associated with obesity-related traits .
Individuals who are homozygous for the high-risk alleles weigh roughly 3 kg more than those individuals homozygous for
the low-risk allele . Homozygosity appears to occur in roughly 16% of several populations that have been studied. The
product of this gene appears to be an enzyme that is likely involved in demethylation of single-stranded DNA in
hypothalamic nuclei involved in regulating energy balance .
Farooqi and co-workers have been looking for alterations in the leptin receptor (LEPR) gene in individuals with severe
early-onset obesity, especially those who were the product of consanguineous families. They found that 3% of 300 of these
subjects had missense or nonsense mutations of the LEPR. Although this rate of gene abnormalities is substantially higher
than the prevalence of mutations of the leptin gene, it still accounts for an extremely small number of cases of obesity.
CAUTION:. The amount of weight gain associated with these genes, although statistically significant, is fairly small,
suggesting either that the environment plays a substantial role it the current epidemic of obesity.
An innovative study by Christakis and Fowler examined data the Framingham Heart Study: who were asked to identify
their friends in an effort to facilitate long-term follow-up and retention in that study. The investigators used these data on
over 12,000 interconnected individuals followed for more than 30 yr to examine the effects of relationships on weight gain.
They found that a person’s risk of becoming obese over the period of follow-up increased by 57% if one of their friends
became obese. The effect was present but of smaller magnitude if the social contact was a sibling or spouse..
Gordon and colleagues found that intestinal bacteria appear to have an important effect on body weight. Two recent papers
in mice ) and human subjects: They found that the intestinal flora of obese mice and human subjects are enriched in
firmicutes species and relatively deficient in bacteroidetes. They further found that transplantation of intestinal flora from
obese mice to lean mice promoted weight gain. In obese humans who lost weight, intestinal flora began to look more like
that of lean individuals, raising questions as to whether these changes are primary or secondary to some aspect of the diet
or energy balance.
34
Which of these clinical features is not part
of this syndrome described by this
pathologist from Mayo Clinic?
A.
B.
C.
D.
Autosomal Dominant
Islet cell tumors
Adrenal and/or
testicular tumors
Cardiac myxomas
M. Srivastava MD, 10/7/2009
Dermatology Online Journal 10 (3): 11
The Story of Discovery
of the Carney Triad
by J. Aidan Carney, M.D., Ph.D., F.R.C.P.I., F.R.C.P.
Sometimes it is strange how events turn out. Dr. E.G. Harrison, a colleague in pathology at Mayo Clinic, died unexpectedly on July 4th
1974. One of his interests was a tumor called paraganglioma. Paragangliomas arise from little groups of cells (minute organs) located in
certain areas of the body, the adrenal gland, and the carotid and vagal bodies in the neck, for example. They are usually benign.
Sometimes, they secrete a chemical (adrenaline) that causes high blood pressure.
In November, 1975 Dr. ER, a pathologist in Iowa, not knowing of Dr. Harrison’s passing, sent him histologic slides because of his special
interest in paraganglioma. The slides were from a 25-year-old woman, Ms. AB, who, without warning, vomited a large amount of blood
(massive hematemesis) and fainted. She was taken to the local hospital where emergency surgery (a partial gastrectomy) was performed to
control the gastric hemorrhage. Dr. ER, on examining the stomach specimen in the laboratory, found 5 tumors, several of which were
ulcerated, the cause of the patient’s gastric hemorrhage. The microscopic examination of the tumor cells revealed unusual patterns,
including their arrangement in clusters. The patient’s history revealed that fourteen years previously, at age 11, she had a tumor excised
from her neck – a paraganglioma of the carotid body. Because of the microscopic similarity between the carotid body paraganglioma and
the gastric tumors, Dr. ER tentatively concluded that the stomach tumors were the result of metastases from the carotid body
paraganglioma that had been carried by the blood stream from the neck to the stomach. Wishing for a second opinion, she sent the
histological slides of the stomach tumors to Dr. Harrison.
Because I had taken up Dr. Harrison’s interest in paragangliomas, the slides were referred to me. And so began my involvement with a
previously unrecognized disorder that was later titled the Carney triad. When I examined the slides in the microscope, I could see the
reason for Dr. ER's diagnosis – the microscopic clustering pattern of the gastric tumor cells mimicked the pattern of paraganglioma.
However, the sequence of events, as related by Dr. ER, namely, the occurrence of a carotid body paraganglioma in an 11-year-old girl (an
age at which tumors are unlikely), followed by the apparent development of gastric metastases (an organ very rarely the seat of metastasis),
after a very long interval (14 years is an unusually long time for metastases to develop), seemed improbable. I thought it more likely that
carotid body tumor (paraganglioma) and gastric tumors (which I interpreted as epithelioid leiomyosarcomas – the term in use in 1975 for
tumors now referred to as GISTs) were different although their microscopic appearances overlapped.
Further, because of the unlikely occurrence of two different and unusual tumors in a young patient (not the time of life when tumors are
ordinarily found), and in whom one of the tumors was multiple (the gastric tumor), I thought that the tumors might be have a connection,
one to the other. But this was just a guess, based on findings in one case. To prove a relationship, it would be necessary to identify
additional similar cases.
I gave Dr. ER my opinion that the gastric tumors were epithelioid leiomyosarcomas and not metastatic paraganglioma. She then told me
that she had learned something new about the patient – that she had five pulmonary tumors, three in one lung and two in the other! I was
taken aback by this news –now this young patient had tumors in 3 organs. In an effort to explain the new finding, I suggested that the
pulmonary tumors were probably spread (metastases) of the gastric tumors to the lung. I discussed the case with a colleague, Dr. Dave
Ahmann, an oncologist, who suggested that the pulmonary nodules should be biopsied to confirm that they were metastases before starting
chemotherapy.
The findings in the case had raised the intriguing question in my mind – could there possibly be a connection between paraganglioma and
gastric epithelioid leiomyosarcoma (GIST)? I thought it worthwhile getting an answer to this – but it would mean going through all Mayo
Clinic records of patients with paraganglioma and all patients with gastric epithelioid leiomyosarcomas (which, before computerization,
would have been a very time-consuming task) to identify other, if any, patients with both tumors. Since I was working on another project at
the time, I could not take up the search immediately. But fortune smiled on me. Shortly afterwards, I met Dr. Sheldon Sheps, the Mayo
Clinic expert on paraganglioma. I mentioned Ms. AB’s case to him and my feeling that there might be possibly a connection between the
patient’s 2 tumors, the carotid body paraganglioma and the GISTs. Had he come across any such case? He couldn’t recall one but he sent
me his list of Mayo Clinic patients who had paraganglioma and another different tumor. The list included 12 patients. Three of them,
young women, had gastric GISTs in addition to paraganglioma! When I checked their records, I found that 2 of the 3 also had benign lung
cartilaginous tumors!
Immediately, I realized 2 things: first, that there almost certainly existed a previously unrecognized disorder (syndrome) that included
paraganglioma and gastric GIST and, second, that the syndrome likely included cartilaginous tumors of the lung also. Straightaway, I
called Dr. ER to tell her this and my strong suspicion that Ms. AB’s lung masses were benign cartilaginous tumors. Her response was
35
55 y.o. post-menopausal woman with a backache. X-ray and Tc
Bone scan as shown. Alk Phos 610 U/L. 6 months after drug
therapy, Calcium now 8.3 mg/dl and phosphorus of 2.8 mg/dl.
ALP now 198. What is the likely cause of her hypocalcemia?
A.
B.
C.
D.
E.
Drug associated vitamin D
malabsorption
Paget’s disease
Unmasking of occult
vitamin D deficiency
Drug induced
hypoparathyroidism
Secondary to drug induced
hypomagnesemia
Endo Prac 2008;14:255
10/7/2009
36
40 y.o. woman has incidental right adrenal mass. Hx. Of back pain
and hypertension. Urinary metanephrines and normetanephrines
slightly above normal. T1-weighted MRI showed a 4 X 2.5 X 2 cm
adrenal mass. No T1 out-of-phase loss of signal and no T2
hypersensitivity. On removal, right adrenal stained positively for
synaptophysin.
A.
B.
C.
D.
Pheochromocytoma
Adrenal lipoma
Ganglioneuroma
Adrenal cancer
10/7/2009
Endo Prac 2008;14:254
Seenia V. Peechakara A1, Leo Aish A2, Michael A. Blake A3, Ann T. Sweeney A1
A1 The Department of Medicine, Caritas St. Elizabeth's Medical Center, Boston,
Massachusetts
A2 The Department of Pathology, Caritas St. Elizabeth's Medical Center, Boston,
Massachusetts
A3 Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts
Ganglioneuromas are rare tumors arising from neural crest cells in sympathetic ganglia or
adrenal medulla. Elevated catecholamines are not typically elevated.
Tumor has Schwann cell staining for S-100 protein and ganglion cells stain for
synaptophysin.
37
Which of these statements is
FALSE re. anorexia nervosa?
A.
B.
C.
D.
Dysrhythmias are more common and may
be due to hypokalemia.
Amenorrhea is due to premature ovarian
failure.
Up to 1/3 of anorectic women have
reported fractures. Estrogen replacement
does not reverse bone loss.
Mortality is 12 times the rate for healthy
young women.
10/7/2009
38
Which of these can misleadingly
elevate Chromogranin A levels?
A.
B.
C.
D.
Aspirin
Beta Blockers
H2- antihistamine agents
Proton-Pump Inhibitors
10/7/2009
May be a good marker for non-secretory paraganglioma or for metastatic
paraganglioma..
Small pheos may nto produce that much CgA.
Renal insufficiency and Proton pump inhibitors can elevate CgA levels.
CgA is also not specific: may be elevated with MTC, carcinoid, and cancers of lung,
prostate, breast and pancreas.
39
Which of these has not been
associated with obesity?
A.
B.
C.
D.
E.
Melanocortin-4 receptor deficiency
Leptin deficiency
Leptin resistance
Leprechaunism
Albright’s hereditary osteodystrophy
10/7/2009
40
Which of the following is FALSE
re. Klinefelter Syndrome?
A.
B.
C.
D.
Is associated with impaired
spermatogenesis but normal testosterone
production.
Males are typically tall with decreased
libido and small testes.
FSH elevation is greater than LH levels.
Inhibin B levels are very low.
Affected individuals have evidence of a
Barr body.
10/7/2009
41
Which of the following is TRUE
re. gestational diabetes?
A.
B.
C.
D.
Screen with a random 50 gm GTT at 12
weeks, in a normal pregnancy.
A 1 hour post-50 gm GTT glucose of 160
mg/dl suggests the need for a repeat 50 gm
GTT 4 weeks later.
Fasting plasma glucose should be less
than 95 mg/dl.
A 2 hour 100 gm GTT is the definitive
test.
10/7/2009
Do screening 50 gm GTT at presentation if previous gestational dm, + family history,
unexplained stillbirth, prior infant with congenital anomaly,prior infant greater than 4 kg,
maternal age > 25, obesity with BMI > 27, glucosuria and hypertension.
FBG should be less than 95.
If screenign test is abnormal ( 1hour glucose > 130 - 180, then do a 100 gm 3hour GTT: 0 < 95, 1 hr- < 180, 2 hr < 155 and 3 hr- < 140
42
Amiodarone may be associated
with ALL of the below EXCEPT:
A.
B.
C.
D.
Decrease thyroid hormone secretion
Increase thyroid hormone secretion
Decrease TSH levels directly
Block T4 to T3 conversion
10/7/2009
Reduce TSH: dopamine and dopamine agonists, steroids, octreotide, bexarotene (retinoid Xreceptor ligand)
Decrease thyroid hormone secretion: thionamides, iodine, amiodarone, alpha interferon,
interleukin 2, lithium, aminoglutethemide, Sunitinib
(in iodine sufficient areas)
Increase thyroid hormone secretion: iodine, amiodarone, lithium, alpha interferon and
interleukin 2 (in iodine deficient areas)
Block T4 to T3 conversion: PTU, amiodarone, propanalol, dexamethasone, iopanoic acid or
sodium ipodate
43