Endocrine disease Flashcards
(158 cards)
1
Q
I. Normal Pituitary:
• Function
A
- the “master gland”
- regulates most other endocrine glands
- connected to hypothalamus via stalk which releases factors controlling release of trophic hormones
2
Q
I. Normal Pituitary:
• Embryology
A
- anterior lobe derived from the primitive oral cavity (Rathke’s Pouch)
- posterior lobe derived from neuroectoderm
3
Q
I. Normal Pituitary:
• Anatomy
A
- contained within the sella turcica of the sphenoid bone
- connected to hypothalamus via stalk → regulation of pituitary hormones
- anterior lobe is composed of round cells arranged in cords and nests
- posterior lobe: composed of modified glial cells and axonal processes extending from hypothalamic neurons
- Hypothalamic neurons produce oxytocin, antidiuretic hormone (ADH)
4
Q
somatotroph
A
growth hormone (GH)
5
Q
lactotroph
A
prolactin (PRL)
6
Q
corticotroph
A
corticotropin (ACTH)
7
Q
gonadotroph
A
Luteinizing hormone (LH) Follicle stimulating hormone (FSH)
8
Q
thyrotroph
A
thyrotropin (TSH)
9
Q
Anterior Lobe Pathology
A. Hyperfunction (hyperpituitarism)
A
o almost always associated with a pituitary adenoma
o may produce symptoms by hormone production or by local mass effect
• compression of optic nerve leading to visual disturbances
• increased intracranial pressure (headache, nausea, vomiting)
10
Q
ACTH and other POMC-derived peptides
associated syndrome
A
Cushing syndrome
Nelson syndrome
11
Q
GH
associated syndrome
A
Gigantism (children)
Acromegaly (adults)
12
Q
Prolactin
associated syndrome
A
Galactorrhea and amenorrhea (females)
Sexual dysfunction, infertility
13
Q
Prolactin & GH
associated syndrome
A
Combined features of prolactin and GH
excess
14
Q
TSH
associated syndrome
A
Hyperthyroidism
15
Q
FSH, LH
associated syndrome
A
Hypogonadism, mass effects and
hypopituitarism
16
Q
POMC:
A
Pro-opiomelanocortin
17
Q
B. Prolactinomas more noticeable in
A
women than in men; can grow to be very large in men before they are noticed.
18
Q
C. With Growth Hormone adenomas, depends on when the
A
epiphyses closes. Patients with acromegaly will have a prognathic mandible, spacing of dentition, large sausage-like fingers, hypertension, and congestive heart failure.
19
Q
B. Hypofunction (hypopituitarism)
A
• may manifest as a deficiency of one hormone or multiple hormones
20
Q
Hypopituitarism: • causes:
A
o nonfunctional pituitary adenoma
o Ischemic necrosis, most commonly from Sheehan’s syndrome (postpartum infarct). Need over 75% of anterior lobe to be destroyed for clinically significant effects.
o Ablation of pituitary by surgery or radiation
o destruction by adjacent tumor
21
Q
Hypopituitarism: • manifestations
A
o Pituitary dwarfism (GH) o Amenorrhea and infertility in women and decreased libido, impotence, and lack of pubic/axillary hair in men (gonadotropin) o No post-partum lactation (prolactin) o Hypothyroidism (TSH) o Hypoadrenalism (ACTH)
22
Q
Posterior lobe pathology
A
• Oxytocin- no significant clinical abnormalities
• Antidiuretic hormone (ADH)
o Functions in kidneys to promote resorption of free water
o diabetes insipidus
23
Q
Gigantism:
• Caused by an
A
adenoma in the anterior lobe that secretes growth hormone
24
Q
Gigantism: • Occurs before
A
closure of the epiphyseal plates (growth plates) in the long bones
25
Gigantism: • Clinical features:
* Generalized increase in the size of the body
| * Arms and legs are disproportionately long
26
Gigantism: • Treatment:
surgical removal of the adenoma
| • Prognosis: fair to good
27
Acromegaly:
| • Increased
growth hormone secretion (also due to an adenoma)
| • After closure of the epiphyseal plates (skeletal maturity)
28
Acromegaly: • Clinical features:
* Enlarged bones of the hands, feet, and face
* Prognathism, development of a diastema
* Hypertension and congestive heart failure may be seen
29
Acromegaly: • Treatment:
same as gigantism (remove adenoma)
| •
30
Acromegaly: Prognosis:
Guarded—due to complications of hypertension and congestive heart failure
31
c. Pituitary Dwarfism:
| • Potential causes:
* Failure of pituitary gland to produce growth hormone
* Lack of response to growth hormone by the patient’s tissues
works
32
c. Pituitary Dwarfism: • Clinical features:
* Short stature
| * Small jaws and teeth
33
c. Pituitary Dwarfism:
| • Treatment:
if lack of production of growth hormone is the problem, then hormone replacement therapy
34
c. Pituitary Dwarfism: • Prognosis:
Good (if replacement therapy works)
35
I. Normal Thyroid: Function
o Produces hormones that regulate the rate at which the body carries out its necessary functions
36
I. Normal Thyroid
| • Anatomy
o Located in the middle of the lower neck, below the larynx and above the clavicles
o “Bow tie” shape
37
I. Normal Thyroid
| • embryology
o develops from an invagination of endoderm which arises at the base of the tongue, in the region of the foramen cecum
o migrates caudually to its location anterior and inferior to the thyroid cartilage
38
I. Normal Thyroid
| • histology
o follicles filled with colloid and lined by cuboidal follicular cell
o small nests of C-cells scattered between the follicles; not visible without special stains
39
II. Hyperthyroidism
| • Most common causes are
o Graves disease (Diffuse toxic hyperplasia) (#1 cause)
o ingestion of excessive exogenous thyroid hormone (TH)
o hyperfunctional multinodular goiter
o hyperfunctional thyroid adenoma
o TSH-secreting pituitary adenoma (Rare)
40
II. Hyperthyroidism
| • Clinical manifestations-
Hypermetabolic state, Overactivity of the sympathetic nervous system
o Hypermobility (increased activity—can’t sit still)
o G-I hypermobility, malabsorption and diarrhea
o Tachycardia, palpitations, irritability
o Nervousness, tremor, irritability, proximal myopathy
o Wide, staring gaze with eyelid lag
o Exophthalmos (bulging of the eyes) with Graves’ disease
o Heat intolerance and excessive sweating
o Soft, warm, flushed skin
o Weight loss despite increased appetite
41
II. Hyperthyroidism:
| o Thyroid Storm
* Abrupt onset of hyperthyroidism usually triggered by stress
* Patients can die of cardiac arrhythmia if untreated – A medical emergency
* Treatment: Depends on the cause. Reactive iodine can be used to destroy overactive thyroid tissue
* Prognosis: Good (If identified and treated properly)
42
II. Hyperthyroidism:
| • Diagnosed by
elevated TH and decreased TSH (primary hyperthyroidism)
43
Graves’ Disease
• female predominance, F:M 7:1
o Common, 1.5-2% of US women
• hyperthyroidism; exophthalmos (40%); skin lesions
o pretibial myxedema, scaly thickening of skin overlying shins
• autoimmune, significant genetic component
o Autoantibodies to TSH receptor; constantly stimulated
44
Graves' disease
| • pathology
o diffuse enlargement of the thyroid on gross examination
o hyperplasia of follicles with lymphoid infiltrates
o Increase in serum free TH, decreased serum TSH
45
III. Hypothyroidism:
o Primary or secondary
46
III. Hypothyroidism:
| o Common causes
o Ablation by surgery or radiation therapy
o Hashimoto thyroiditis (Autoimmune destruction)
o Iodine deficiency
47
III. Hypothyroidism:
| o Clinical manifestations
Cretinism
| o Myxedema
48
III. Hypothyroidism:
| o Measure serum TSH
o Increased in primary due to loss of feedback inhibition
| o Not increased in cases caused by primary hypothalamic or pituitary disease
49
III. Hypothyroidism: o Treatment:
Thyroid hormone replacement therapy (Synthroid)
50
Hypothyroidism: o Prognosis:
Good unless treatment is delayed. The damage to skeletal and nervous systems could be permanent
51
o Cretinism
* Develops in childhood
* Rare now due to iodine supplementation in diet
* Impaired development of skeleton and CNS
* Coarse facial features
* Short stature
* Severe mental retardation
* Protruding tongue
52
o Myxedema
* Develops in older children and adults
* Generalized apathy and mental sluggishness (mimics depression)
* Cold-intolerance, obese
* Coarse facial features, enlargement of tongue, deepening of voice, constipation, late cardiac effects
* Accumulation of mucopolysaccharide-rich edema
53
Hashimoto Thyroiditis
o female predominance, 10:1 to 20:1
o usually older women
o significant genetic component
o Most common cause of hypothyroidism where dietary iodine is sufficient
o Autoimmune; progressive destruction of parenchyma with inflammatory infiltrates
o Involves CD4+, CD8+, and NK cells
54
Hashimoto thyroiditis: o initially
euthyroid, with progression of disease most patients will become hypothyroid
o Painless thyroid enlargement with hypothyroidism
55
Hashimoto thyroiditis: o Some cases are preceded by
transient hyperthyroidism
56
Hashimoto thyroiditis: o Patients usually at risk for
other autoimmune diseases and B-cell Non-Hodgkin lymphomas
57
Hashimoto thyroiditis: o No established risk of
development of thyroid neoplasm
58
Goiters
| • Most common manifestation of
thyroid disease
59
Goiters: • Diffuse and multinodular goiters reflect
impaired synthesis of thyroid hormone
60
Goiters: o Most often due to
dietary deficiency, though some cases are idiopathic
61
Goiters: o Impairment of
TH synthesis → increase in serum TSH → hypertrophy and hyperplasia of thyroid follicular cells → gross enlargement of gland
62
Goiters: • Most common clinical features are due to
```
mass effects
o Cosmetic problem
o Airway obstruction
o Dysphagia
o Compression of vessels
```
63
Goiters: • Hyperfuctional,
“toxic’ goiter
o In a minority of patients, the a “toxic” nodule may develop in a long-standing, non-toxic goiter
o Hyperthyroidism
64
Thyroid Neoplasms
| o solitary thyroid nodules may be detected in
2-4% of the general population
65
Thyroid Neoplasms: o most nodules are
non-neoplastic disease (1% are carcinomas)
66
Thyroid Neoplasms: o Nodules in young patients are
more likely to be neoplastic
67
Thyroid Neoplasms: o Nodules in males are more likely to be
neoplastic
68
Thyroid Neoplasms: o genetic and environmental factors
o exposure to radiation in first 2 decades
69
Follicular Adenoma
o solitary nodules, 3-5 cm in diameter
o grossly separated from the normal thyroid by a thin, discrete capsule
o microscopically composed of follicles with varying amounts of colloid
70
0
| Papillary Thyroid Carcinoma
o accounts for >85% of thyroid cancers
o 3rd-5th decade, F>>M
o 60-70% are multifocal
o some cases related to radiation exposure
o Many have mutations in the RET proto-oncogene
71
Papillary thyroid carcinoma: o Pathology
o microscopically characterized by papillary projections
o distinctive nuclear changes
o nuclear clearing, aka “orphan annie nuclei”
o nuclear grooves
o nuclear inclusions
o nuclear enlargement
72
Papillary thyroid carcinoma: o Indolent lesions,
10-year survival rates >95%
| o poor prognostic features include extrathyroidal extension and elderly
73
Follicular Carcinoma
o accounts for 5-15% of thyroid cancers
o Older age than papillary; areas with dietary iodine deficiency
o grossly may resemble an adenoma with a discrete capsule
o Must see invasion through the capsule or into the blood vessels
74
Anaplastic Thyroid Carcinoma
o Rare <5%; typically presents as rapid enlargement in a long standing goiter
o extremely poor prognosis
75
Medullary Thyroid Carcinoma
o uncommon, accounts for 5% of thyroid cancer
o derived from the parafollicular (C) cells
o may be sporadic or familial (component of MEN syndromes)
o All have mutation in the RET proto-oncogene
o Increased serum calcitonin
76
Parathyroid Glands
I. Normal
o embryology
o Derived from the third and fourth pharyngeal pouches
77
Parathyroid Glands
I. Normal
o anatomy
o typically 4 parathyroid glands, 1 at each corner of the posterior surface of the thyroid
78
Parathyroid Glands
I. Normal
o histology
o composed mostly of chief cells (principal cells, clear cells), secrete PTH
o oxyphil cells; unknown function
79
Parathyroid Glands
I. Normal
o PTH
o Decreased levels of free calcium in the bloodstream stimulate the synthesis and secretion of PTH, with the following effects
• Increase in renal tubular reabsorption of calcium
• Increase in urinary phosphate excretion
• Increase in the renal conversion of vitamin D into its active form, which in turn increases gastrointestinal calcium absorption
• Increase in osteoclastic activity which releases calcium from the bones
o Net effect: increase in the level of free calcium, which inhibits further PTH secretion
80
II. Hyperparathyroidism
| • An important cause of
hypercalcemia
81
Hyperparathyroidism: • Excessive secretion of
parathyroid hormone (PTH)
82
Hyperparathyroidism:
| • Two types
o Primary: an autonomous spontaneous overproduction of PTH
| o Secondary: a secondary phenomenon in patients with chronic renal failure
83
Hyperparathyroidism: • Treatment:
Surgical removal of hyperplastic parathyroid glands. Kidney transplant may be beneficial in patients with hyperparathyroidism secondary to renal failure.
84
Hyperparathyroidism: • Prognosis:
Usually good
85
Primary hyperthyroidism:
| o Common
endocrine disorder generally affecting adults
| hyperparathyroidism
86
Primary hyperthyroidism:o Caused by
parathyroid adenomas or hyperplasia → hypercalcemia
| o Clinical features
87
Primary hyperthyroidism:: o More common in
women (4:1); often clinically silent
88
Primary hyperthyroidism:: o Classic constellation of symptoms
o Currently, routine blood tests taken for other reasons often detect clinically silent
• Painful bones: Fractures associated with osteoporosis
• Renal stones
• Abdominal groans: Constipation, peptic ulcers, and gallstones
• Psychic moans: Refers to depression, lethargy and seizures
o Weakness and fatigue
o Brown tumor of hyperparathyroidism can develop in the jaws
o Ground glass appearance
o Metastatic calcifications
• Deposition of calcium in throughout body, including blood vessels
89
Secondary hyperthyroidism:
• Renal failure is most common cause
90
Secondary hyperthyroidism: o Decreased phosphate excretion
→ hyperphosphatemia → depresses serum calcium levels → stimulates parathyroid glands (which become hyperplastic)
91
Secondary hyperthyroidism: • Normally kidneys would increase
Vit D synthesis to increase Ca absorption in gut to compensate
• But because they aren’t working, there is decreased renal synthesis of Vitamin D and reduced intestinal absorption of calcium
92
Secondary hyperthyroidism:: • Symptoms are dominated by renal PTH sustains serum calcium
failure
93
Secondary hyperthyroidism: • Same manifestations as
primary HPT, but usually less severe
| • Bone changes- renal osteodystrophy
94
Secondary hyperthyroidism: • Serum calcium remains
near normal because the compensatory increase in
95
III. Hypoparathyroidism
• Uncommon
• Etiology
o surgical removal of parathyroids (inadvertently during thyroidectomy or other neck dissection)
o congenital absence (DiGeorge’s syndrome)
o auto-immune disease
96
Hypoparathyroidism: • Clinical manifestations
o Hypocalcemia
o Increased neuromuscular excitability
o Cardiac arrhythmias
o Increased intracranial pressure and seizures
97
Normal Pancreas
| • Embryology
o arises from endoderm of the foregut
98
Pancreas: • Histology
• Islets of Langerhans –clusters of endocrine cells interspersed among the acinar groups that make up the exocrine pancreas
99
Pancreas: • The pancreas has both
exocrine and endocrine functions. The exocrine pancreas makes gastric enzymes.
100
Pancreas: • Cell types:
```
cell type hormonal product
beta insulin
alpha glucagon
delta somatostatin
PP pancreatic polypeptide (VIP)
```
101
beta
insulin
102
alpha
glucagon
103
delta
somatostatin
104
PP
pancreatic polypeptide (VIP)
105
o Glucagon:
mobilizes carbohydrates (stored in the liver) into circulation when the body needs them. Promotes glycogenolysis and gluconeogenesis in fasting states.
106
o Insulin:
Major anabolic hormone, many synthetic and growth-promoting effects - allows glucose to be transported and stored in cells within the body after meals
107
o Somatostatin:
suppresses both insulin and glucagon release
108
o VIP: exerts
several G-I effects
109
• Normal Insulin Physiology & Glucose Homeostasis
| Homeostasis depends on 3 processes:
o Gluconeogenesis
o Glucose uptake by tissues
o Actions of insulin & glucagon
=
110
Insulin increases the rate of
glucose transport into certain cells of the body
111
Diabetes Mellitus
| • Group of metabolic disorders resulting in
hyperglycemia (excessive amounts of glucose in the blood) due to defects in insulin secretion, insulation action, or both
• In 2015, over 30 million Americans affected (7 % of population) with ¼ undiagnosed, with 84 million pre-diabetics
• Vasculopathy with long-term complications involving kidneys, eyes, nerves
• Leading cause of end-stage renal disease (ESRD), blindness, and amputation
112
Classification
| • Type 1
(aka juvenile onset or insulin dependent diabetes mellitus)
o 5% of cases
o Severe insulin deficiency
113
• Type 2 (aka adult onset or non-insulin dependent)
o Caused by a combination of peripheral resistance to insulin action and an inadequate response to insulin secretion by the beta cells.
114
Presenting symptoms of DM
| • Type 1
o Symptoms appear once 90% of beta cells have been destroyed, usually by age 20
o Polyuria
o Polydipsia
o Polyphagia with weight loss
o Ketoacidosis
• With fat as primary energy source: excess ketones in blood, low blood pH
• Can lead to diabetic coma
115
Presenting symptoms of DM
| • Type 2
o Usually present after age 40, but not always
o Polyuria and polydipsia may occur
o Diagnosis usually made by routine blood or urine tests
o Enhanced susceptibility of infections, periodontal disease
116
Laboratory DM diagnosis
| • Normal glucose is
70-120mg/dL
| • Random blood glucose concentration of 200mg/dL or higher
117
DM diagnosis: • Fasting glucose greater than
126mg/dL on more than one occasion
| • Blood glucose greater than 200mg/dL within 2 hours of ingesting 75g of glucose (oral glucose tolerance test)
118
Type 1 DM
* Absolute lack of insulin secondary to autoimmune destruction of beta cells
* Abrupt onset
* Patients require insulin from outside sources to survive or kidney/pancreas transplantation
* Prognosis is guarded due to many complications
119
Type 2 DM
| • Results from a
collection of multiple genetic defects, each contributing its own predisposing risk and modified by environment.
• Peripheral tissues cannot respond properly to insulin (insulin resistance)
120
Type 2 DM: • Beta cell dysfunction results in
inadequate insulin secretion in the face of insulin resistance and hyperglycemia.
121
Type 2 DM: • Disposing factors
o Obesity
• 80% of Type 2 DM patients are obese
• 60% of the obese exhibit glucose intolerance
• Obesity in children is implicated in development of DM as adults
• Exercise and weight loss can reverse insulin resistance and clinical evidence of disease
o Pregnancy
o Stress
122
Type 2 DM: • Treatment:
Weight loss, improve diet, oral hypoglycemic drugs, insulin
123
Type 2 DM: • Prognosis is
fair. Patients have complications similar to those seen in Type I. However, the disease is usually not as severe. Type I patients are more likely to die of the disease than type II patients.
124
Manifestations of DM
| • In pancreas
o Reduction of the number and size of islets
o Heavy inflammatory infiltrate
o Amyloid deposition
125
Manifestations of DM:
• Vasculopathy
o Responsible for 80% of DM-related deaths
o Atherosclerosis is severe and accelerated
o Myocardial infarction and stroke
o Gangrene of lower extremities is 100-fold increased over normal population
o Thickened basement membrane, especially around small blood vessels (microangiopathy)
126
Manifestations of DM: • Kidneys (diabetic nephropathy)
o 2nd leading cause behind vascular diseases, leads to HTN and ESRD
o Glomerular lesions
• Diffuse glomerulosclerosis
• 90% of diabetics within 10 years; not specific to diabetics
• Microangiopathy around glomerular capillaries and deposition of matrix
• Proteinuria, total renal failure
o Nodular glomerulosclerosis
• 15-30% of long-term diabetics; specific to diabetics
• Ball-like deposition of matrix at the periphery of the glomerulus
• Total renal failure
• Renal atherosclerosis
• Pyelonephritis
127
Manifestations of DM: • Eye (retinopathy)
o 4th leading cause of blindness
o Microangiopathy and microaneurysms
o Retinal detachment and vision loss
128
Manifestations of DM• Diabetic neuropathy
o Can affect the peripheral sensorimotor nerves
| o Autonomic neuropathy causing disturbances in bowel and bladder function, impotence
129
Manifestations of DM: • Enhanced susceptibility to
infections of the skin, TB, pneumonia, deep fungal infections, pyelonephritis
130
Manifestations of DM: • Causes of death
o Type 1 > Type 2
| o MI, renal failure, cerebrovascular disease, atherosclerosis, infection
131
III. Islet Cell Tumors
| •
Uncommon (<2% of all pancreatic neoplasms)
• Most are from the exocrine pancreas
• may be functional or nonfunctional
• Insulinoma (Insulin Secreting Islet Cell Tumor)
• Beta cell tumor, hyperinsulinism, most are adenomas
• Hypoglycemia quickly occurs from fasting or exercise
• Many are asymptomatic, 5-10% malignant
• Nervousness, confusion, stupor
• Surgical excision
• Gastrinoma
132
Islet Cell tumors: • Arise in
duodenum, peripancreatic tissues, or pancreas
133
With Islet cell tumors, you see:
* gastric acid hypersecretion
| * 90-95% of recalcitrant peptic ulcers
134
• Zollinger-Ellison Syndrome
* Pancreatic islet cell tumor, hypersecretion of gastric acid, severe peptic ulcers
* Most are malignant (60%), surgical resection
135
I. Normal adrenal glands:
• Two triangular-shaped glands located on top of the kidneys
• Adrenal Cortex (outer portion of the gland); weight: 4-5 grams; 3 zones
o zona glomerulosa – mineralcorticoids (aldosterone)
o zone fasciculata – glucocorticoids (cortisol)
o zona reticularis – sex hormones (estrogen/androgen)
• Adrenal Medulla (inner portion of the gland);: neural origin, chromaffin, source of catecholamines (epinephrine, norepinephrine and dopamine)
136
Hypercortisolism (Cushing Syndrome):
• Causes
o Most commonly by excess administration of exogenous glucocorticoids
o Primary adrenal hyperplasia or neoplasm (e.g. adrenal adenoma)
o Primary pituitary source
• ACTH oversecretion by pituitary microadenoma
• Known as Cushing disease
o Ectopic ACTH secretion by neoplasm, e.g. lung
137
Hypercortisolism (Cushing Syndrome):
• Signs and symptoms
o Short Term
* weight gain and hypertension
* “Moon facies” (accumulation of fat in the face)
* “Buffalo hump” (accumulation of fat in the posterior neck and back)
138
Hypercortisolism (Cushing Syndrome):
Signs and symptoms:
o Long Term
* Decreased muscle mass, weakness
* Diabetes
* Osteoporosis
* Cutaneous striae, hirsutism
* Mental disturbances: mood swings, depression, psychosis
* Menstrual irregularities
139
Hypercortisolism (Cushing Syndrome):
• Treatment:
depends on the cause
| • Prognosis: good
140
Hyperaldosteronism
| • Characterized by
chronic excess aldosterone secretion – causes:
o Sodium retention, Potassium excretion
o Hypertension and hypokalemia
141
Hyperaldosteronism: • Primary
o Very rare
o Hyperplasia, neoplasm, idiopathic
o Decreased levels of plasma renin
142
Hyperaldosteronism: • Secondary
o Aldosterone release in response to activation of renin-angiotensin system
o Increased levels of plasma renin
143
III. Hypoadrenalism
* Primary or
* Secondary
* Decreased stimulation of adrenals from deficiency of ACTH
144
Hypoadrenalism: • Don’t appear until at least
90% of adrenal gland has been destroyed
145
Hypoadrenalism:
| • Manifestations
• Fatigue
• GI disturbances (anorexia, nausea, vomiting, weight loss, diarrhea)
- weakness
146
Acute Adrenocortical Insufficiency
| •
In patients maintained on exogenous corticosteroids, rapid withdrawal of steroids or failure to increase steroids in response to an acute stress can precipitate an adrenal crisis
• Vomiting, abdominal pain, hypotension, coma, death
147
Acute Adrenocortical Insufficiency
• Can also be caused by adrenal hemorrhage or stress in a patient with existing Addison's
148
Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)
* Progressive destruction of adrenal cortex
* Serum ACTH may be elevated → skin and mucosal pigmentation
* Destruction of cortex prevents response to ACTH
* Potassium retention, sodium loss, hyperkalemia, hyponatremia, volume depletion, and hypotension
149
Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)
• Causes
o Autoimmune destruction of steroid-producing cells
• Most common, 60-70% of cases
o TB
o AIDS
o Metastatic disease
• Clinical features
• Progressive weakness—easily fatigued
• GI disturbances: nausea, vomiting, anorexia, weight loss, diarrhea
• Hyperpigmentation—often involves the oral mucosa
• A craving for salt
150
Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)
• Treatment:
Corticosteroid replacement therapy
151
Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)
• Prognosis:
Guarded. Can result in death if not recognized and treated properly
152
Secondary Adrenocortical Insufficiency
• Any disorder of hypothalamus of pituitary that reduces output of ACTH
• Symptoms similar to Addison’s disease
o But no skin/mucosa pigmentation
153
Adrenal Neoplasms
* Pheochromocytoma
| * Multiple Endocrine Neoplasia (MEN) Syndromes
154
• Pheochromocytoma
| o neoplasm of
chromaffin cells, F > M, 30-60 yrs.
155
Chromaffin cells produce
epinephrine.
156
Pheochromoctyoma:
o Hypertension, tachycardia, tremor, headache
o Surgically correctible
o rule of 10's: 10 % bilateral, extra-adrenal, malignant, familial syndromes
o large polygonal cells with variable pleomorphism
157
• Multiple Endocrine Neoplasia (MEN) Syndromes
```
• Types I, 2A, and 2B
• Tumors of multiple endocrine organs
o Medullary Thyroid Carcinoma
o Pheochromocytoma
o Parathyroid
o Pituitary
o Pancreas
• RET proto-oncogene
```
158
• MEN 2B notable for early orofacial manifestations
o Mucosal neuromas (tongue, labial commisure)
o Large, blubbery lips
o Marfanoid body habitus
o Early onset medullary carcinoma of thyroid
