Quiz 3, Endocrine Flashcards
1
Q
What occurs as a result of excess secretion of trophic pituitary hormones?
A
Hyperpituitarism
2
Q
What is the most common cause of hyperpituitarism?
A
Adenoma arising in the anterior lobe
3
Q
What occurs as a result of deficiency in one or more of the hormones produced by the pituitary gland?
A
Hypopituitarism
4
Q
What are the causes of HYPERpituitism?
A
Pituitary adenoma
hyperplasia and carcinomas of the anterior pituitary
secretion of hormones by non-pituitary tumors
certain hypothalamic disorders
5
Q
What are the causes of HYPOpituitarism?
A
Destructive processes such as: ischemic injury surgery or radiation inflammatory reactions non-functional pituitary adenomas
6
Q
Expanding pituitary lesions often compress what? Causing what?
A
The decussating fibers in the optic chiasm causing visual field abnormalities, MC the lateral fields (bitemporal hemianopsia)
7
Q
What is the size criteria for a pituitary adenoma being micro or macro? Which are more common?
A
> 10 mm
MC: Micro (16.7% of people, mostly undiagnosed)
8
Q
T/F: ectopic pituitary adenomas are common.
A
False
They are rare tumors, occurring outside the sella turcica (usually in sphenoid sinus, suprasellar region, nasopharynx and the cavernous sinuses)
9
Q
Why are silent and hormone-negative adenomas more likely to be macroadenomas, as opposed to micro?
A
Because they come to clinical attention at a later stage because they are not associated with endocrine abnormalities.
10
Q
How are pituitary adenomas classified?
A
By what type of hormone is secreted by the tumor. (Tumors that don’t secrete any active hormone are still sometimes called chromophobic)
Based on plasma hormone levels or on immunohistochemical staining.
11
Q
What is the peak age of incidence of pituitary adenomas?
A
35-60
12
Q
What are the gross characteristics of a typical pituitary adenoma?
A
Soft, well-circumscribed lesion confined to the sella turcica.
13
Q
What is the microscopic appearance of a pituitary adenoma?
A
Uniform polygonal cells arrayed in sheets or cords (cytoplasms may be acidophilic, basophilic, or chromophobic)
14
Q
What distinguishes a pituitary adenoma from non-neoplastic anterior pituitary parenchyma?
A
The cellular monomorphism and the absence of a significant reticulin network.
15
Q
What are the most frequent type of functioning pituitary adenomas, accounting for ~30% of all clinically recognized cases?
A
Prolactinoma (lactotroph adenoma)
16
Q
Prolactinomas have a propensity to undergo what kind of changes?
A
Dystrophic calcification, ranging from isolated psammoma bodies to extensive calcification of virtually the entire tumor mass (pituitary stone)
17
Q
Why are prolactinomas more readily diagnosed in women of childbearing age?
A
The hyperprolactinemia disrupts menses and causes amenorrhea, galactorrhea, loss of libido, and infertility. Men and menopausal women have more subtle symptoms which allows the tumors to reach considerable size
18
Q
The majority of prolactinomas are composed of what type of cells?
A
Weakly acidophilic or chromophobic cells (sparsely granulated). Rarely, strongly acidophilic.
19
Q
Adenomas of the anterior pituitary gland are a major clinical feature of what form of inherited endocrine disorder?
A
Multiple endocrine neoplasia type 1 (MEN 1)
20
Q
What structures are most often affected by MEN syndromes?
A
Parathyroid glands
Pancreatic islet cells
Anterior lobe of the pituitary
21
Q
What is pituitary apoplexy?
A
Acute hemorrhage or infarction into an adenoma (80% of cases involve previously undiagnosed adenomas)
22
Q
What are the sxs of pituiray apoplexy?
A
Starts with a HA, then a rapidly worsening visual field defect. Then acute adrenal insufficiency sxs.
23
Q
What is caused by necrosis of the pituitary gland due to blood loss and hypovolemic shock during and after childbirth?
A
Sheehan syndrome (postpartum hypopituitarism)
24
Q
What causes Sheehan syndrome?
A
Hypertrophy and hyperplasia of lactotrophs during pregnancy results in the enlargement of the anterior pituitary without a corresponding increase in blood supply. It is also supplied by a low pressure portal venous system that is vulnerable to hemorrhages or hypotensions leading to ischemia. (posterior pituitary is not effect due to its direct arterial supply)
25
T/F: empty sella is gangsta' slang for "we're out of wine"
False! It means the sella turcica is without its homey, the pituitary gland. It just gets filled with CSF.
26
T/F: Amyloid deposits may be seen in pituitary adenomas in the absence of amyloidosis.
True
27
What are the two most common hypothalamic suprasellar tumors?
Gliomas and craniopharyngiomas
28
What is the most common sellar tumor in children? Hint: it's benign but locally invasive and originates from remnants of Rathke's pouch.
Craniopharyngioma (bimodal age distribution; 5-15 and 65+)
29
What are the microscopic characteristics of craniopharyngiomas?
Expanding mass arising in the sella turcica that erodes bone and infiltrates into surrounding structures. Appear as squamous and columnar epithelium lining cystic space filled with oily fluid and "wet keratin".
30
Although pituitary adenomas are widely invasive, destructive of adjacent tissues, and lethal, they are not classified as malignancies. How are malignant tumors of adenohypophyseal origin defined?
Their ability to metastasize
31
What are the two most common sources of cancer that metastasizes to the pituitary?
Breast and lung cancers
32
What is the literal translation of "filet mignon"?
Cute cut
33
What are some of the effects of T3 excess?
```
Increased HR
vasodilation
warm, smooth, moist skin
Increased GI motility
Increased bone turnover
Increased muscle contraction
```
34
What are the conditions most notable for causing a HYPOthyroid state?
```
Hashimoto's
Acute thyroiditis
Subacute "
Infiltrative "
Postoperative
Iatrogenic
```
35
What is the most common cause of hypothyroidism?
Autoimmune lymphocytic thyroiditis (Hashimoto's)
36
What is the relationship of iodine to the thyroid gland?
Iodine is essential for the production of thyroxine. If deficient in the diet, the thyroid becomes enlarged (goiter)
37
One cause of HYPERthyroidism is the conscious or accidental ingestion of excess quantities of thyroid hormone. What is this called?
Thyrotoxicosis factitia
38
What are some of the conditions that cause HYPERthyroidism?
```
Grave's dz
Toxic thyroid nodule
Plummer's dz (toxic multinodular goiter)
Iatrogenic hyperthyroidism
Thyroid storm
```
39
What condition is an autoimmune dz in which the thyroid gland is attacked by a variety of cell and antibody mediated immune processes?
Hashimoto's thyroiditis
40
What is the cause of thyroid enlargement in Hashimoto's?
Lymphocytic infiltration and fibrosis (not hypertrophy)
41
Physiologically, antibodies against what, causes gradual destruction of follicles in the thyroid gland with Hashimoto's?
Thyroid peroxidase (TPO) and/or thyroglobulin
42
What is the gross appearance of Hashimoto's thyroiditis?
Cut surface may have "fleshy" appearance
Retrosternal extension
Enlargement is not necessarily symmetrical
Lobulated pattern
Scattered tiny nodules of darker tan colored glassy material (residual colloid)
43
T/F: Hashimoto's can cause both HYPER and HYPOthyroidism
True: Early on it causes hyper, than goes through euthyroid stage. Eventually atrophy of the gland results in hypothyroidism.
44
What is a cell that often appears in thyroid tissue of patients with Hashimoto's or follicular thyroid cancer?
Hurthle cell
45
What do Hurthle cells look like?
Enlarged epithelial cells which generally stain pink with abundant eosinophilic granular cytoplasm as a result of altered mitochondria
46
Does subacute thyroiditis cause HYPO or HYPERthyroidism?
Either
47
What histologic finding is characteristic of de Quervain's disease (sub-acute thyroiditis)?
Granulomas (Multinucleated giant cells)
48
What is the most common location for a thyroglossal cyst?
Between the isthmus of the thyroid and the hyoid bone
49
What is the most common type of congenital neck malformation and what causes it?
A thyroglossal duct cyst caused by duct being persistent (failing to close) during embryonic development. It becomes fluid filled.
50
T/F: Thyroid nodules are rare and indicate malignancy.
False. They are common, but benign (95%).
51
Non-toxic multinodular goiter is compatible with euthyroid state. What is seen microscopically if the follicles are irregularly enlarged?
They are usually surrounded with flattened epithelium, consistent with inactivity of the thyroid.
52
A toxic nodular goiter (TNG) is a thyroid gland that contains what? (aka Plummer's dz)
Autonomously functioning thyroid nodules resulting in hyperthyroidism
53
What do you expect to see in a biopsy of a toxic nodular goiter?
Hypercellularity
54
What is an autoimmune dz caused by long acting thyroid autoantibodies (LATS-Ab) which activate TSH-receptors, thereby stimulating thyroid hormone synthesis and secretion and thyroid growth, causing a diffusely enlarged goiter?
Graves' dz
55
What is the most common cause of hyperthyroidism?
Graves' dz, especially severe hyperthyroidism
56
What population is at risk for Graves' dz?
Usually present in adolescence
Hereditary
5-10x more common in females
57
What is the microscopic characteristic of Graves' dz?
Prominent infoldings of the hyperplastic epithelium
58
What is the risk of a colloid cyst?
They are benign, "cold" nodules, found incidentally, but need to be distinguished from possible carcinoma.
59
T/F: Follicular adenomas contain colloid, but have greater variability in size than normal
True
60
What are the four types of thyroid cancer?
Papillary (MC)
Follicular
Medullary
Undifferentiated/Anaplastic
61
What is the route of metastases for papillary carcinoma?
Lymphatics (which is common)
62
T/F: There is no such thing as a papillary adenoma
True. All papillary neoplasms of the thyroid should be considered malignant
63
What is the microscopic appearance of a papillary carcinoma of the thyroid?
The fronds of tissue have thin fibrovascular cores and have an overall papillary pattern. Psammoma bodies are present.
64
How does follicular carcinoma of the thyroid metastasize?
Hematogenously causing distant spread (more malignant that papillary)
65
What is the gross appearance of Follicular carcinoma of the thyroid?
Encapsulated and solitary, often found in necrotic and/or hemorrhagic areas.
66
What is the microscopic appearance of follicular carcinoma of the thyroid?
Encapsulated, well-defined follicles containing colloid (making it difficult to distinguish from follicular adenoma)
67
What may occur as a sporadic, usually unilateral, condition or as a familial (bilateral) condition transmitted as an autosomal dominant trait?
Medullary carcinoma
68
With medullary carcinoma what is detected in serum and what causes it with a medullary carcinoma?
Proliferation of parafollicular cells (C cells) results in excess amounts of calcitonin
69
What can be seen microscopically with a medullary carcinoma?
Pink hyaline material with the appearance of amyloid.
70
What type of thyroid tumor is the fastest growing and results in death within 1 year of dx in 80% of cases?
Anaplastic carcinoma. It's highly malignant and metastasizes regionally and distantly.
71
What is one of the most common endocrine disorders and is an important cause of hypercalcemia?
Primary hyperparathyroidism
72
What is the most common underlying cause of hyperfunctioning parathyroid conditions?
Adenoma (85-95%)
Primary hyperplasia (5-10)
Carcinoma (~1)
73
How do you distinguish a parathyroid adenoma from normal parathyroid tissue on microscopy?
Lack of adipose tissue
74
What is secondary hyperparathyroidism caused by?
Any condition that gives rise to chronic hypocalcemia which leads to compensatory overactivity of the parathyroid glands
75
What is the most common cause of secondary hyperparathyroidism?
Renal failure
76
What causes depressed serum calcium levels, resulting in overactivity of the parathyroid glands?
Chronic renal insufficiency is associated with decreased phosphate excreted in the urine which results in hyperphosphatemia. This also impacts the synthesis of active vit-D which reduces absorption of calcium in the gut.
77
How do you distinguish parathyroid carcinoma?
It's rare, sxs are more severe and sudden onset. However, it cannot be confirmed before surgery.
78
Malignancy related hypercalcemia, most commonly, results from what?
Ectopic production of PTH-like hormone from the tumor cells
79
PTH related protein (PTHrP) can be secreted by many types of cancer cells but is seen most commonly with breast and certain types of lung cancer. PTHrP related hypercalcemia is sometimes the first sign of the malignancy. What is this symptomatology called?
Para-neoplastic syndrome
80
What condition has unexplained hypokalemia as well as hypernatremia and hypertension, while cortisol is normal?
Primary hyperaldosteronism (Conn's syndrome)
81
What is the usual cause of primary hyperaldosteronism?
A functional adrenal adenoma (may also be due to adrenal hyperplasia)
82
What do labs reveal in a Conn's syndrome patient?
High serum sodium and aldosterone
Low serum potassium
Decreased plasma renin
83
Cushing's syndrome (adrenal hyperfunction) is caused by what two types of things and which is more common?
MC - long term use of pharmacologic glucocorticoids
| Tumors
84
Pituitary tumors involving the corticotroph cell line result in excess ACTH production. What is this called?
Cushing's disease
85
Adenomas with what layer of the adrenals can result in excess production of cortisol which can lead to primary cushing's syndrome?
Zona fasiculata
86
T/F: non-pituitary and non-adrenal tumors can also result in Cushing's syndrome as a result of ectopic ACTH production.
True. Carcinoma of the lung is MC
87
T/F: ACTH independent Cushing's syndrome is more common.
False. 80% are dependent
88
What is the most common cause of primary Addison's disease?
Autoimmune destruction of the adrenal cortex
89
What lab profile do you except in a patient with Addison's disease?
Extremely low cortisol
Extremely high ACTH
hypoglycemia, hyponatremia, hyperkalemia
90
What causes the hyperpigmentation seen in primary Addison's?
Increased ACTH which stimulates melanocytes to produce more melanin.
91
What is usually the cause of secondary Addison's?
Inadequate secretion of ACTH by the anterior pituitary. (may also be due to pituitary trauma, surgery, irradiation, tumors or withdrawal from exogenous corticosteroid use)
92
Secondary Addison's can result from hemorrhage into the adrenal gland. What is this called?
Waterhouse-Frederickson syndrome
93
Patients with secondary Addison's exhibit similar symptoms as primary, except what notable difference and why?
Skin pallor rather than hyperpigmentation because secondary has diminished ACTH
94
Why might an Addisonian crisis occur?
Exogenous glucocorticoids will suppress ACTH production. If there is an abrupt withdrawal, the pituitary will be unable to compensate. It can also occur at times of great stress (surgery or infection).
95
What condition accounts for 95% of cases of congenital adrenal hyperplasia, which is an inborn error of metabolism resulting in a deficiency of enzymes that synthesize cortisol?
21-Hydroxylase deficiency
96
Why does 21-Hydroxylase deficiency lead to virilization of female patients?
Blocking of cortisol leads to shunting of cortisol precursors. In particular 17-hydroxyprogesterone is increased with a subsequent increase in androstenedione (an androgen)
97
What is the most pathological condition associated with the adrenal medulla?
Pheochromocytoma
98
What is pheochromocytoma and what is the hallmark symptom?
A catecholamine secreting tumor of the chromaffin cells within the adrenal medulla.
Hypertension that may be variable and very labile.
99
T/F: Autopsy studies show that ~5-15% of the general adult population may have adrenal incidentalomas.
True. They are biochemically and clinically asymptomatic adrenal masses.
100
What is the definitive criteria for adrenal malignancy?
Findings of distant metastasis or of local tumor invasion. (only 1% of adrenal tumors are malignant)
101
What cancer originates from neural crest cells, most often arise from the adrenal glands but may be seen anywhere along the sympathetic chain, and is essentially a sarcoma of the nervous system?
Neuroblastoma
102
What is the most common, solid, extra-cranial malignancy in infants and children?
Neuroblastoma
103
What is a characteristic microscopic finding of neuroblastomas?
Rosettes (circular groupings of dark tumor cells surrounding a pale staining center composed of neurofibrils)
104
What is the underlying feature of all forms of diabetes mellitus?
Hyperglycemia
105
What is the fasting blood glucose criteria for DM?
> 126 mg/dl
106
What is the non-fasting blood glucose criteria for DM?
> 200 mg/dl
107
What is the HgbA1C criteria for DM?
> 6.5%
108
What term is used to describe when a sugar molecule bonds to a protein or lipid without the controlling action of an enzyme?
Glycation
109
Which type of primary diabetes is most common?
Type 2 DM (~85-95%)
110
What are some causes of secondary diabetes?
Pancreatitis/injury, pancreatectomy, hemochromatosis
Gestational diabetes
Cushings, acromegaly, glucagonoma, pheochromocytoma
Glucocorticoids, diuretics, oral contraceptives
Insulin receptor site defets
111
What condition is an autoimmune disease in which islet destruction is caused primarily by immune effector cells reacting against endogenous beta-cell antigens?
Type 1 DM (formerly known as juvenile diabetes)
| MC develops in childhood, manifests at puberty, progresses with age.
112
What notable antibodies are found in Type 1 DM?
Islet cell Abs
Anti-insulin Abs
Abs are directed against Glutamic acid decarboxylase (GAD)
113
What do you expect to see on a micrograph of a type 1 DM islet cell?
Lymphocytic infiltration
114
What are the two metabolic defects in Type 2 DM?
Insulin resistance
| Beta-cell dysfunction (inadequate insulin secretion)
115
Under a microscope what doe the islets of Langerhans demonstrate in a Type 2 DM pt?
Hyalinization with deposits of amorphous material (amyloid)
116
If a patient appears to have type 2 DM, but is not obese, what dx should you consider?
Late-onset Autoimmune Diabetes Mellitus (DM 1.5)
117
What are the five subdivisions of neuropathy in patients with type 2 DM?
```
Sensorimotor
Autonomic
GI autonomic
Genitourinary autonomic
Hypoglycemic unawareness
```
118
What leads to incompetence of vascular walls seen in diabetic retinopathy?
Hyperglycemia induced intramural pericyte death and thickening of the basement membrane.
119
What is characteristic of non-proliferative diabetic retinopathy?
Dilated capillaries (micro aneurisms) which leak RBCs and plasma into the substance of the retina.
120
What is the most common cause of visual loss due to diabetic retinopathy?
Macular edema, which is caused by leakage from retinal capillary microaneurisms
121
What characterizes proliferative diabetic retinopathy?
Non-proliferative type progresses and the lack of oxygen results in new growth of blood vessels that are fragile and rupture, causing various problems.
122
What is seen on a micrograph in a patient with diabetic nephropathy?
Nodular glomerulosclerosis. Diffuse increase in mesangial matrix and acellular nodules.
123
What is the earliest microscopically detectable change in the course of diabetic nephropathy?
Thickening of the capillaries within the glomerulus
124
T/F: pancreatic endocrine tumors are common
False. 1:100,000
125
A micrograph of a pancreatic islet cell reveals cells that are monotonous and demonstrate minimal pleomorphism or mitotic activity. There is also amyloid deposition. The patient experienced episodic hypoglycemia. What is the dx?
Insulinoma
126
What is Whipple's triad?
1. Sx caused by hypoglycemia
2. Low plasma glucose at time of sx
3. Sx are relieved when glucose is restored
127
What is the most common type of pancreatic endocrine tumors (which are rare)? Where do 99% of them originate?
Insulinoma, the pancreas.
128
Where do malignant gastrinomas most commonly spread?
Liver and lymph nodes near the pancreas and SI
129
Gastrinomas are frequently the source of the excess gastrin found in patients with what condition?
Zollinger-Ellison syndrome
130
How did you know it was beets?
It's always beets
