B3 Endocrine pathology Flashcards
Anterior Pituitary:
What is a pituitary adenoma?
A benign tumor of the anterior pituitary cells that can be functional (hormone-producing) or non-functional (no hormones)
A benign tumor of the anterior pituitary cells that can be functional (hormone-producing) or non-functional (no hormones)
pituitary adenoma
What is a non-functional anterior pituitary adenoma?
Presents with:
1) Bitemporal hemianopsia (compressed optic chiasm)
2) Hypopituitarism (compressed normal pituitary tissue)
3) Headaches
Presents with:
1) Bitemporal hemianopsia (compressed optic chiasm)
2) Hypopituitarism (compressed normal pituitary tissue)
3) Headaches
non-functional anterior pituitary adenoma
What is a functional anterior pituitary adenoma?
Tumors that secrete hormones & are dependent on the kinds of hormones they produce
Prolactinoma, Growth hormone cell adenoma, ACTH cell adenomas, LH adenomas, FSH adenomas & TSH cell adenoma etc
Tumors that secrete hormones & are dependent on the kinds of hormones they produce
Prolactinoma, Growth hormone cell adenoma, ACTH cell adenomas, LH adenomas, FSH adenomas & TSH cell adenoma etc
functional anterior pituitary adenoma
What is a prolactinoma?
The most common functional adenoma of the anterior pituitary gland. It presents with:
1) Galactorrhea
2) Amenorrhea (females)
3) Low libido (men)
4) Headaches
The most common functional adenoma of the anterior pituitary gland. It presents with:
1) Galactorrhea
2) Amenorrhea (females)
3) Low libido (men)
4) Headaches
prolactinoma
How do you treat a prolactinoma?
1) Dopamine agonists like bromocriptine or cabergoline to suppress prolactin production to shrink the tumor
2) Surgery to remove larger lesions
1) Dopamine agonists like bromocriptine or cabergoline to suppress prolactin production to shrink the tumor
2) Surgery to remove larger lesions
Are the treatment options for which tumor?
prolactinoma
How does a Growth hormone cell adenoma present in children?
In children in presents as gigantism
1) Increased linear growth epiphyses that aren’t fused
In children it presents as gigantism
1) Increased linear growth epiphyses that aren’t fused
Growth hormone cell adenoma present in children
How does a Growth hormone cell adenoma present in adults?
In adults it presents as acromegaly
1) Enlarged bones (hands, feet, & jaw)
2) Enlarged organs causing dysfunction (Organomegaly i.e cardiac failure)
3) Enlarged tongue (macroglossia)
4) Secondary Diabetes Mellitus (GH induces liver gluconeogenesis)
In adults it presents as acromegaly
1) Enlarged bones (hands, feet, & jaw)
2) Enlarged organs causing dysfunction (Organomegaly i.e cardiac failure)
3) Enlarged tongue (macroglossia)
4) Secondary Diabetes Mellitus (GH induces liver gluconeogenesis)
Growth hormone cell adenoma present in adults
What are the treatment options for Growth Hormone cell adenoma?
1) Octreotide (a somatostatin analog that suppresses GH levels)
2) GH receptor antagonists
3) Surgery
1) Octreotide (a somatostatin analog that suppresses GH levels)
2) GH receptor antagonists
3) Surgery
Are treatment options for which type of tumor?
Growth Hormone cell adenoma
Acromegaly (adults) or Gigantism (children) presents with elevated GH & IGF1 that can’t be suppressed by oral glucose indicates which condition?
Growth hormone cell adenoma
What is an ACTH cell adenoma?
It secretes too much ACTH (elevated cortisol) causing cushing syndrome
It secretes too much ACTH (elevated cortisol) causing cushing syndrome
ACTH cell adenoma
What is Hypopituitarism?
When there’s insufficient hormone production by the anterior pituitary gland. Symptoms start appearing when over 75% of the pituitary parenchyma is lost
When there’s insufficient hormone production by the anterior pituitary gland. Symptoms start appearing when over 75% of the pituitary parenchyma is lost
Hypopituitarism
What are 4 things that can cause Hypopituitarism?
1) Pituitary adenomas (adults)
2) Craniopharyngiomas (children)
3) Sheehan syndrome (preggos)
4) Empty sella syndrome
1) Pituitary adenomas (adults)
2) Craniopharyngiomas (children)
3) Sheehan syndrome (preggos)
4) Empty sella syndrome
Can all cause which condition?
Hypopituitarism
How can pituitary adenomas (adults) & Craniopharyngiomas (children) cause hypopituitarism?
They cause a mass effect of pituitary apoplexy (bleeding into the adenoma)
What is Sheehan syndrome & why does it cause hypopituitarism?
A condition in pregnancy that causes the pituitary gland to enlarge & then have blood loss during parturition which worsens the infarct. It presents as:
1) Poor lactation
2) Loss of pubic hair
3) Fatigue
A condition in pregnancy that causes the pituitary gland to enlarge & then have blood loss during parturition which worsens the infarct. It presents as:
1) Poor lactation
2) Loss of pubic hair
3) Fatigue
Sheehan syndrome in pregnancy causing hypopituitarism
What is Empty Sella syndrome & how does it cause hypopituitarism?
A congenital Sella defect that causes the arachnoid & CSF to herniate into the sella which compresses the pituitary gland destroying it
Imaging shows an empty sella (absent pituitary)
A congenital Sella defect that causes the arachnoid & CSF to herniate into the Sella which compresses the pituitary gland destroying it
Imaging shows an empty Sella (absent pituitary)
Empty Sella syndrome
What is Central Diabetes Insipidus?
ADH deficiency caused by issues with the hypothalamic or posterior pituitary resulting in free water loss (trauma/inf/inflam/tumor)
Presents with:
1) Polyuria & Polydipsia
2) Hypernatremia & high serum osmolality
3) Low urine osmolality & specific gravity
Tests:
Water deprivation doesn’t increase urine osmolality
Rx. Give desmopressin (an ADH analog)
ADH deficiency caused by issues with the hypothalamic or posterior pituitary resulting in free water loss (trauma/inf/inflam/tumor)
Presents with:
1) Polyuria & Polydipsia
2) Hypernatremia & high serum osmolality
3) Low urine osmolality & specific gravity
Tests:
Water deprivation doesn’t increase urine osmolality
Rx. Give desmopressin (an ADH analog)
Central Diabetes Insipidus
Low levels of ADH & a water deprivation doesn’t increase urine osmolality, what is the condition?
Central Diabetes insipidus
What is Nephrogenic Diabetes Insipidus?
Impaired renal response to ADH (normal release) because of inherited mutations or as a side effect of drugs (lithium or demeclocycline)
Same signs as CDI:
1) Polyuria & Polydipsia
2) Hypernatremia & high serum osmolality
3) Low urine osmolality & specific gravity
But there is NO response to desmopressin
Impaired renal response to ADH (normal release) because of inherited mutations or as a side effect of drugs (lithium or demeclocycline)
Same signs as CDI:
1) Polyuria & Polydipsia
2) Hypernatremia & high serum osmolality
3) Low urine osmolality & specific gravity
But there is NO response to desmopressin
Nephrogenic Diabetes Insipidus
What is SIADH?
Excessive secretion of ADH from the posterior pituitary that is usually due to small cell carcinoma of the lung (others being CNS trauma, pulmonary infection or drugs (cyclophosphamide)). That results in the retention of free water.
Presents as:
1) Hyponatremia & low serum osmolality
2) Mental status changes & seizures
(too much free water causes neuronal swelling & cerebral edema)
Rx:
Free water restriction or Demeclocycline
Excessive secretion of ADH from the posterior pituitary that is usually due to small cell carcinoma of the lung (others being CNS trauma, pulmonary infection or drugs (cyclophosphamide)). That results in the retention of free water.
Presents as:
1) Hyponatremia & low serum osmolality
2) Mental status changes & seizures
(too much free water causes neuronal swelling & cerebral edema)
Rx:
Free water restriction or Demeclocycline
SIADH
What is a thyroglossal duct?
It is cystic dilation of the thyroglossal duct remnant in the thyroid gland that presents as an anterior neck mass
It is cystic dilation of the thyroglossal duct remnant in the thyroid gland that presents as an anterior neck mass
thyroglossal duct
What is a lingual thyroid?
It is the persistence of thyroid tissue at the base of the tongue that presents as a base of tongue mass
It is the persistence of thyroid tissue at the base of the tongue that presents as a base of tongue mass
lingual thyroid
What is Hyperthyroidism?
What is it:
What are the symptoms:
A dysfunctional thyroid gland causes elevated T3 & T4 (despite low TSH). This causes
1) Increased BMR due to increased synthesis of Na+/K+ ATPase
2) Increased sympathetic nervous system activity due to elevated B1 adrenergic receptors
1) Weight loss (despite a good appetite)
2) Heat intolerance & sweating
3) Tachycardia & increased CO
4) Arrythmias (A fIb esp in elderly)
5) Tremors, Anxiety, Insomnia
6) Staring gaze with lid lag
7) Diarrhea & malabsorption
8) Oligomenorrhea
9) Bone resorption with hypercalcemia
10) Muscle mass wasting & weakness
11) Hypocholesterolemia
12) Hyperglycemia (increased gluconeogenesis & glycogenolysis)
A dysfunctional thyroid gland causes elevated T3 & T4 (despite low TSH). This causes
1) Increased BMR due to increased synthesis of Na+/K+ ATPase
2) Increased sympathetic nervous system activity due to elevated B1 adrenergic receptors
1) Weight loss (despite a good appetite)
2) Heat intolerance & sweating
3) Tachycardia & increased CO
4) Arrythmias (A fIb esp in elderly)
5) Tremors, Anxiety, Insomnia
6) Staring gaze with lid lag
7) Diarrhea & malabsorption
8) Oligomenorrhea
9) Bone resorption with hypercalcemia
10) Muscle mass wasting & weakness
11) Hypocholesterolemia
12) Hyperglycemia (increased gluconeogenesis & glycogenolysis)
Hyperthyroidism
What is a possible complication of hyperthyroidism (regarding the bones)?
Osteoporosis
What causes Exophthalmos & Pretibial Myxedema in Graves disease?
Fibroblasts behind the orbit & overlying the shin express TSH receptors. When activated they cause a buildup of glycosaminoglycans (made of chondroitin sulfate & hyaluronic acid), inflammation, fibrosis, & edema leading to both exophthalmos & pretibial myxedema
Increased uptake of 131I aka hot nodule would indicate which 2 possible conditions?
Graves or a nodular goiter
A type 2 hypersensitivity reaction where the body makes autoantibodies (IgG) that stimulate TSH receptors increasing thyroid hormone levels. It usually happens in women 20-40yrs & it’s the most common cause of hyperthyroidism.
Presents with:
1) Hyperthyroidism
2) Diffuse goiter
3) Exophthalmos & Pretibial myxedema
Histology shows:
1) irregular follicles with scalloped colloid
2) chronic inflammation in the thyroid gland
Labs show:
1) Elevated total & free T4
2) Hypocholesterolemia
3) Elevated serum glucose
Rx B-blockers, Thioamide, & Radioiodine ablation
Complication:
Thyroid storm
Graves disease
Graves disease
What is it:
What are the symptoms:
What are the histological findings:
What are the lab findings:
What are the treatment options:
What is a complication of the condition:
A type 2 hypersensitivity reaction where the body makes autoantibodies (IgG) that stimulate TSH receptors increasing thyroid hormone levels. It usually happens in women 20-40yrs & it’s the most common cause of hyperthyroidism.
Presents with:
1) Hyperthyroidism
2) Diffuse goiter
3) Exophthalmos & Pretibial myxedema
Histology shows:
1) irregular follicles with scalloped colloid
2) chronic inflammation in the thyroid gland
Labs show:
1) Elevated total & free T4
2) Hypocholesterolemia
3) Elevated serum glucose
Rx B-blockers, Thioamide, & Radioiodine ablation
Complication:
Thyroid storm
What is a thyroid storm?
What is it:
What are the symptoms:
What are the treatment options:
Elevated catecholamines & massive excess of hormones in response to stress. It presents as:
1) Arrythmia
2) Hyperthermia
3) Vomiting with hypovolemic shock
Treatment:
Propylthiouracil (reduces T4 conversion to T3), B-blockers, & steroids
Elevated catecholamines & massive excess of hormones in response to stress. It presents as:
1) Arrythmia
2) Hyperthermia
3) Vomiting with hypovolemic shock
Treatment:
Propylthiouracil (reduces T4 conversion to T3), B-blockers, & steroids
Thyroid storm
What is a multinodular goiter?
what is it:
What is a rare complication:
An enlarged thyroid gland with multiple nodules caused by iodine deficiency it is usually non-toxic (euthyroid)
Complication:
rarely progresses to a toxic goiter
An enlarged thyroid gland with multiple nodules caused by iodine deficiency it is usually non-toxic (euthyroid)
Complication:
rarely progresses to a toxic goiter
Multinodular goiter
What is a toxic goiter?
A rare complication of Multinodular goiter that occurs when regions of the thyroid can become TSH independent causing elevated T4 & hyperthyroidism
A rare complication of Multinodular goiter that occurs when regions of the thyroid can become TSH independent causing elevated T4 & hyperthyroidism
Toxic goiter
What is cretinism?
What are the symptoms:
What are the causes:
Hypothyroidism in neonates or infants that presents as:
1) Mental retardation
2) Short stature & skeletal anomalies
3) Coarse facial features
4) Macroglossia (enlarged tongue)
5) Umbilical hernia
Causes:
1) Maternal hypothyroidism during early pregnancy
2) Thyroid agenesis (neonate/infant)
3) Dyshormonogenetic goiter (congenital issue with thyroid peroxidase)
4) Iodine deficiency
Hypothyroidism in neonates or infants that presents as:
1) Mental retardation
2) Short stature & skeletal anomalies
3) Coarse facial features
4) Macroglossia (enlarged tongue)
5) Umbilical hernia
Causes:
1) Maternal hypothyroidism during early pregnancy
2) Thyroid agenesis (neonate/infant)
3) Dyshormonogenetic goiter (congenital issue with thyroid peroxidase)
4) Iodine deficiency
Cretinism
Hypothyroidism in adults & older children causing a lower BMR & reduced sympathetic activity
Presents with:
1) Weight gain (despite normal appetite)
2) Slowed mental activity
3) Muscle weakness
4) Cold intolerance & reduced sweating
5) Bradycardia with reduced CO (SOB)
6) Oligomenorrhea
7) Hypercholesterolemia
8) Constipation
It is most commonly caused by Iodine deficiency & Hashimoto’s thyroiditis. Other causes include drugs (lithium), surgery, & radio ablation of the thyroid
Myxedema
Myxedema
What is it:
What are the symptoms
What causes it:
Hypothyroidism in adults & older children causing a lower BMR & reduced sympathetic activity
Presents with:
1) Weight gain (despite normal appetite)
2) Slowed mental activity
3) Muscle weakness
4) Cold intolerance & reduced sweating
5) Bradycardia with reduced CO (SOB)
6) Oligomenorrhea
7) Hypercholesterolemia
8) Constipation
Causes:
Iodine deficiency & Hashimoto’s thyroiditis
Other causes include drugs (lithium), surgery, & radio ablation of the thyroid
Hashimoto thyroiditis
What is it:
What are the symptoms:
What are the histological findings:
What is a complication:
It is autoimmune destruction of the thyroid that is associated with an HLA-DR5 genotype. It is the most common cause of hypothyroidism in places with enough iodine
Presents with:
1) Starts as hyperthyroidism (because of follicle damage) that progresses to hypothyroidism (low T4 & high TSH)
2) Antithyroglobulin & Antithyroid peroxidase present (indicates thyroid damage)
Histology shows:
1) Chronic inflammation
2) Germinal centers
3) Hurthle cells
Complications:
A higher risk of B cell (marginal zone) lymphoma
It is autoimmune destruction of the thyroid that is associated with an HLA-DR5 genotype. It is the most common cause of hypothyroidism in places with enough iodine
Presents with:
1) Starts as hyperthyroidism (because of follicle damage) that progresses to hypothyroidism (low T4 & high TSH)
2) Antithyroglobulin & Antithyroid peroxidase present (indicates thyroid damage)
Histology shows:
1) Chronic inflammation
2) Germinal centers
3) Hurthle cells
Complications:
A higher risk of B cell (marginal zone) lymphoma
Hashimoto thyroiditis
What genotype is Hashimoto thyroiditis most commonly associated with?
HLA-DR5 genotype
What is subacute granulomatous (De Quervain) thyroiditis?
What is a complication:
Granulomatous thyroiditis after a viral infection. It is usually self limiting & presents as a tender thyroid with transient hyperthyroidism
A rare complication is that it can progress to hypothyroidism
Granulomatous thyroiditis after a viral infection. It is usually self limiting & presents as a tender thyroid with transient hyperthyroidism
A rare complication is that it can progress to hypothyroidism
subacute granulomatous (De Quervain) thyroiditis
What is Riedel Fibrosing Thyroiditis?
It is chronic inflammation & fibrosis of the thyroid making it non-tender & “hard as wood”. It can mimin anaplastic carcinoma (but there’s no malignant cells & these patients are younger ~40yrs)
Complication, is that it can spread to local structures (airway)
It is chronic inflammation & fibrosis of the thyroid making it non-tender & “hard as wood”. It can mimin anaplastic carcinoma (but there’s no malignant cells & these patients are younger ~40yrs)
Complication, is that it can spread to local structures (airway)
Riedel Fibrosing Thyroiditis
Which conditions would have decreased uptake of 131I aka a cold nodule?
adenoma or carcinoma (biopsy is warranted)
What is a follicular adenoma?
Benign proliferation of the follicles surrounded by a fibrous capsule (usually non-functional but not always)
Benign proliferation of the follicles surrounded by a fibrous capsule (usually non-functional but not always)
Follicular adenoma
papillary carcinoma?
The most common thyroid carcinoma that is usually caused by exposure to ionizing radiation during childhood.
Histology shows:
Papillae that are lined with clear “orphan Annie eye” nuclei, nuclear grooves, & psammoma bodies
Complications:
It tends to spread to cervical LN but it has an excellent prognosis
The most common thyroid carcinoma that is usually caused by exposure to ionizing radiation during childhood.
Histology shows:
Papillae that are lined with clear “orphan Annie eye” nuclei, nuclear grooves, & psammoma bodies
Complications:
It tends to spread to cervical LN but it has an excellent prognosis
papillary carcinoma
What is follicular carcinoma?
Malignant proliferation of the follicles surrounded by a fibrous capsule with INVASION through that capsule (islands). It usually metastasizes via the blood
Malignant proliferation of the follicles surrounded by a fibrous capsule with INVASION through that capsule (islands). It usually metastasizes via the blood
follicular carcinoma
What is MEN1?
Pituitary tumor
Parathyroid tumor
Pancreatic tumor
Pituitary tumor
Parathyroid tumor
Pancreatic tumor
MEN1
What is the MEN2 Type A tumor?
Due to RET oncogene mutations causing:
Parathyroid tumor
Pheochromocytoma
Medullary thyroid carcinoma
Due to RET oncogene mutations causing:
Parathyroid tumor
Pheochromocytoma
Medullary thyroid carcinoma
MEN2 Type A tumor
What is the MEN2 Type B?
Due to RET oncogene mutations causing:
Mucosal neuromas
Pheochromocytomas
Medullary thyroid carcinoma
Marfan habitus
Due to RET oncogene mutations causing:
Mucosal neuromas
Pheochromocytomas
Medullary thyroid carcinoma
Marfan habitus
MEN2 Type B
medullary carcinoma
What is it:
What are the histological findings:
What are the causes:
What are the treatment options:
Malignant proliferation of parafollicular C cells that secrete calcitonin (causes Ca2+ resorption from blood) causing hypocalcemia. The calcitonin often deposits into the tumor as amyloids
Histology shows:
Sheets of malignant cells in an amyloid stroma
Caused by:
MEN2A & MEN2B Ret oncogene mutations
Rx: Prophylactic thyroidectomy
Malignant proliferation of parafollicular C cells that secrete calcitonin (causes Ca2+ resorption from blood) causing hypocalcemia. The calcitonin often deposits into the tumor as amyloids
Histology shows:
Sheets of malignant cells in an amyloid stroma
Caused by:
MEN2A & MEN2B Ret oncogene mutations
Rx: Prophylactic thyroidectomy
medullary carcinoma
What is an anaplastic carcinoma?
An undifferentiated malignant tumor of the thyroid that is usually seen in the elderly, & it has a poor prognosis.
Complications come from it invading local structures leading to dysphagia or respiratory issues
An undifferentiated malignant tumor of the thyroid that is usually seen in the elderly, & it has a poor prognosis.
Complications come from it invading local structures leading to dysphagia or respiratory issues
anaplastic carcinoma
primary hyperparathyroidism?
What is it:
What are the symptoms:
What are the lab findings:
What is the treatment:
A disorder of the pancreas (usually an adenoma but less likely a carcinoma or sporadic hyperplasia of the parathyroid)
If caused by an adenoma it is usually benign & affects one gland presenting as:
1) Hypercalcemia
2) Nephrolithiasis (calcium oxalate)
3) Nephrocalcinosis (metastatic calcification of renal tubules)
4) Seizures/depression
5) Constipation, Peptic ulcer disease, Acute pancreatitis
6)Osteitis fibrosa cystica (bone resorption causes cystic spaces)
Labs show:
Elevated serum PTH, Ca2+, & alkaline phosphatase
Elevated urine cAMP
Reduced serum phosphate
Rx: Surgery
A disorder of the pancreas (usually an adenoma but less likely a carcinoma or sporadic hyperplasia of the parathyroid)
If caused by an adenoma it is usually benign & affects one gland presenting as:
1) Hypercalcemia
2) Nephrolithiasis (calcium oxalate)
3) Nephrocalcinosis (metastatic calcification of renal tubules)
4) Seizures/depression
5) Constipation, Peptic ulcer disease, Acute pancreatitis
6)Osteitis fibrosa cystica (bone resorption causes cystic spaces)
Labs show:
Elevated serum PTH, Ca2+, & alkaline phosphatase
Elevated urine cAMP
Reduced serum phosphate
Rx: Surgery
primary hyperparathyroidism
What are the lab values expected for Primary hyperthyroidism?
Labs show:
Elevated serum PTH, Ca2+, & alkaline phosphatase
Elevated urine cAMP
Reduced serum phosphate
Labs show:
Elevated serum PTH, Ca2+, & alkaline phosphatase
Elevated urine cAMP
Reduced serum phosphate
lab values expected for Primary hyperthyroidism
Secondary hyperparathyroidism
What is it:
What are the lab findings:
What is a complication:
Excess PTH production due to another disease/pathology. The most common cause is chronic renal disease which reduces phosphate excretion. The elevated serum phosphate binds free calcium triggering the release of more PTH
Labs show:
Elevated serum phosphate, PTH & alkaline phosphatase
Reduces serum Ca2+
Complication arises as renal osteodystrophy
Excess PTH production due to another disease/pathology. The most common cause is chronic renal disease which reduces phosphate excretion. The elevated serum phosphate binds free calcium triggering the release of more PTH
Labs show:
Elevated serum phosphate, PTH & alkaline phosphatase
Reduces serum Ca2+
Complication arises as renal osteodystrophy
Secondary hyperparathyroidism
hypothyroidism
What is it:
What are the symptoms:
What are the lab values:
Low PTH caused by autoimmune damage to the parathyroids, surgical excision, or Di George syndrome.
It presents as:
1) Numbness & Tingling
2) Muscle spasms (tetany) that can be triggered by an inflated BP cuff (trousseaus sign) or tapping the facial nerve (Chvostek sign)
Labs show:
Reduced PTH & serum Ca2+
Low PTH caused by autoimmune damage to the parathyroids, surgical excision, or Di George syndrome.
It presents as:
1) Numbness & Tingling
2) Muscle spasms (tetany) that can be triggered by an inflated BP cuff (trousseaus sign) or tapping the facial nerve (Chvostek sign)
Labs show:
Reduced PTH & serum Ca2+
hypothyroidism
What is pseudohypoparathyroidism?
What are the lab findings:
What are the symptoms:
End organ resistance to PTH that mimics the effects of regular hypoparathyroidism except PTH is actually elevated
Labs show:
Elevated PTH & Hypocalcemia
Signs:
Shorter stature & shorth 4th & 5th digits
End organ resistance to PTH that mimics the effects of regular hypoparathyroidism except PTH is actually elevated
Labs show:
Elevated PTH & Hypocalcemia
Signs:
Shorter stature & shorth 4th & 5th digits
pseudohypoparathyroidism
What is type 1 Diabetes Mellitus?
What are the symptoms:
What are the histological findings:
What is a complication:
Insulin deficiency caused by autoimmune destruction of Beta cells by T lymphocytes. It is associated with the HLA-DR3 & DR4 genotypes.
It presents as:
1) Hyperglycemia (high serum glucose)
2) Weight loss, Low muscle mass, & pOLYPHAGIA
3) Polyuria, Polydipsia, & Glucosuria
Histology shows:
Inflamed pancreatic islets & auto-antibodies against insulin (sign of damage)
Complication is Diabetic Ketoacidosis
Insulin deficiency caused by autoimmune destruction of Beta cells by T lymphocytes. It is associated with the HLA-DR3 & DR4 genotypes.
It presents as:
1) Hyperglycemia (high serum glucose)
2) Weight loss, Low muscle mass, & pOLYPHAGIA
3) Polyuria, Polydipsia, & Glucosuria
Histology shows:
Inflamed pancreatic islets & auto-antibodies against insulin (sign of damage)
Complication is Diabetic Ketoacidosis
type 1 Diabetes Mellitus
What is Diabetic Ketoacidosis?
What are the causes:
What are the symptoms:
What are the lab findings:
What are the treatment options:
A complication of diabetes (1) that results in excessive serum ketone levels.
causes
1) stress/infection causing epinephrine to stimulate glucagon to increase lipolysis making more FFAs. The liver turns FFAs into ketone bodies (B-hydroxybutyric acid & acetoacetic acid)
It presents as:
1) Fruity breath
2) Kussmaul respirations
3) N/V
4) Mental status changes
Labs show:
1) Hyperglycemia (>300mg/dL)
2) Anion gap metabolic acidosis
3) Hyperkalemia
Rx:
Fluids, insulin, & electrolytes
A complication of diabetes (1) that results in excessive serum ketone levels.
It is usually triggered by stress/infection causing epinephrine to stimulate glucagon to increase lipolysis making more FFAs. The liver turns FFAs into ketone bodies (B-hydroxybutyric acid & acetoacetic acid)
It presents as:
1) Fruity breath
2) Kussmaul respirations
3) N/V
4) Mental status changes
Labs show:
1) Hyperglycemia (>300mg/dL)
2) Anion gap metabolic acidosis
3) Hyperkalemia
Rx:
Fluids, insulin, & electrolytes
Diabetic Ketoacidosis
What is type 2 diabetes mellitus
What are the risk factors:
What are the symptoms:
What are the lab findings:
What are the complications:
What are the treatment options:
The most common form of diabetes. It is caused by end-organ resistance to insulin. It is usually seen in middle-aged obese adults & starts with elevated insulin levels until Beta cells become exhausted.
Risks include obesity (less insulin receptors) & genetics
It presents as:
1) Polyuria
2) Polydipsia
3) Hyperglycemia
Labs show:
Random glucose >200mg/dL
Fasted glucose >126mg/dL
Glucose tolerance test >200mg/dL 2hrs post glucose loading
Complication is a hyperosmolar non-ketotic coma
Rx:
Diet/exercise
Drugs (sulfonylurea & metformin)
Exogenous insulin
The most common form of diabetes. It is caused by end-organ resistance to insulin. It is usually seen in middle-aged obese adults & starts with elevated insulin levels until Beta cells become exhausted.
Risks include obesity (less insulin receptors) & genetics
It presents as:
1) Polyuria
2) Polydipsia
3) Hyperglycemia
Labs show:
Random glucose >200mg/dL
Fasted glucose >126mg/dL
Glucose tolerance test >200mg/dL 2hrs post glucose loading
Complication is a hyperosmolar non-ketotic coma
Rx:
Diet/exercise
Drugs (sulfonylurea & metformin)
Exogenous insulin
Type 2 Diabetes Mellitus
What is a hyperosmolar non-ketotic coma?
A complication of Diabetes (2) where blood glucose is over 500mg/dL which leads to life threatening diuresis, hypotension, & coma. There are NO ketones due to the low levels of circulating insulin.
A complication of Diabetes (2) where blood glucose is over 500mg/dL which leads to life threatening diuresis, hypotension, & coma. There are NO ketones due to the low levels of circulating insulin.
hyperosmolar non-ketotic coma
What is a long-term complication of diabetes?
- Non-enzymatic glycosylation of blood vessels:
- Osmotic damage
Non-enzymatic glycosylation of large & medium blood vessels can result in which long term complications of diabetes?
- peripheral vascular disease (amputations)
- Atherosclerosis resulting in cardiovascular disease
Non-enzymatic glycosylation of small blood vessels can result in which long term complications of diabetes?
1) Hyaline arteriosclerosis of the renal arteriole’s involvement leads to glomerulosclerosis causing small/scarred kidneys with a granular surface
2) Hyaline arteriosclerosis of the efferent renal arteriole involvement leads to glomerular hyperfiltration injury with microalbuminuria that progresses to nephrotic syndrome with Kimmelstiel-Wilson nodules in the glomeruli
what is a marker of glycemic control?
Non-enzymatic glycosylation of hemoglobin produces glycated hemoglobin (HbA1c)
Osmotic damage can result in which long term complications of diabetes?
Glucose can freely enter Schwann cells, Pericytes of retinal blood vessels, & the lens. Then aldose reductase converts glucose to sorbitol, resulting in:
1) osmotic damage
2) peripheral neuropathy
3) impotence
4) blindness/cataracts
What is an insulinoma?
What are the symptoms:
What are the lab values:
What is the treatment:
a pancreatic endocrine tumor of the islet cells that is usually due to MEN1.
It presents with
1) Episodic hypoglycemia
2) Mental status changes
Labs show:
Reduced Serum glucose <50mg/dL
Elevated Insulin & C-peptide
Rx: Give glucose
a pancreatic endocrine tumor of the islet cells that is usually due to MEN1.
It presents with
1) Episodic hypoglycemia
2) Mental status changes
Labs show:
Reduced Serum glucose <50mg/dL
Elevated Insulin & C-peptide
Rx: Give glucose
insulinoma
Labs show:
Reduced Serum glucose <50mg/dL
Elevated Insulin & C-peptide
Insulinoma
What is a gastrinoma?
a pancreatic endocrine tumor of the islet cells that is usually due to MEN1.
It presents with
1) Peptic ulcers that are resistant to treatment (Zollinger-Ellison syndrome) that can be multiple & in the jejunum
a pancreatic endocrine tumor of the islet cells that is usually due to MEN1.
It presents with
1) Peptic ulcers that are resistant to treatment (Zollinger-Ellison syndrome) that can be multiple & in the jejunum
Gastrinoma
What is a Somatostatinoma?
A pancreatic endocrine tumor of the islet cells that is usually due to MEN1, that inhibits gastrin & cholecystokinin.
Presents with:
1) Achlorhydria (inhibited gastrin)
2) Cholelithiasis & Steatorrhea
(inhibited cholecystokinin)
A pancreatic endocrine tumor of the islet cells that is usually due to MEN1, that inhibits gastrin & cholecystokinin.
Presents with:
1) Achlorhydria (inhibited gastrin)
2) Cholelithiasis & Steatorrhea
(inhibited cholecystokinin)
Somatostatinoma
What is a VIPoma?
A pancreatic endocrine tumor of the islet cells that secretes vasoactive intestinal peptide. It is usually due to MEN1.
It presents with:
1) Watery diarrhea
2) Hypokalemia
3) Achlorhydria
A pancreatic endocrine tumor of the islet cells that secretes vasoactive intestinal peptide. It is usually due to MEN1.
It presents with:
1) Watery diarrhea
2) Hypokalemia
3) Achlorhydria
VIPoma
What is Hyperaldosteronism?
What are the symptoms:
What is the diagnostic test:
What are the treatment options:
When the glomerulosa produces excess aldosterone which acts on the CCT & DCT to increase Na+ & K+ absorption. It can be primary (low renin & no edema) or secondary (high renin & edema).
It presents as:
1) HTN
2) Hypokalemia
3) Metabolic alkalosis
Diagnosed via CT
Rx: Mineralcorticoid receptor antagonist or surgery to remove an adenoma or carcinoma
When the glomerulosa produces excess aldosterone which acts on the CCT & DCT to increase Na+ & K+ absorption. It can be primary (low renin & no edema) or secondary (high renin & edema).
It presents as:
1) HTN
2) Hypokalemia
3) Metabolic alkalosis
Diagnosed via CT
Rx: Mineralcorticoid receptor antagonist or surgery to remove an adenoma or carcinoma
Hyperaldosteronism
What is primary hyperaldosteronism?
It is usually due to bilateral adrenal hyperplasia or adrenal adenoma (ex. Conn syndrome) or very rarely adrenal carcinoma.
Rx: Mineralcorticoid receptor antagonist or surgery to remove an adenoma or carcinoma
What is secondary hyperaldosteronism?
It happens because of the RAAS activation due to renovascular HTN & CHF
It happens because of the RAAS activation due to renovascular HTN & CHF
secondary hyperaldosteronism
It is usually due to bilateral adrenal hyperplasia or adrenal adenoma (ex. Conn syndrome) or very rarely adrenal carcinoma.
Rx: Mineralcorticoid receptor antagonist or surgery to remove an adenoma or carcinoma
primary hyperaldosteronism
What is Glucocorticoid -remedial aldosteronism (GRA)?
What are the symptoms:
What is the treatment:
A autosomal dominant mutation that leads to familial hyperaldosteronism due to the aberrant expression of aldosterone synthase in the fasciculata.
It classically presents as a child with:
1) HTN
2) Hypokalemia
3) Elevated Aldosteronism
4) Low renin
Rx: Dexamethasone
A autosomal dominant mutation that leads to familial hyperaldosteronism due to the aberrant expression of aldosterone synthase in the fasciculata.
It classically presents as a child with:
1) HTN
2) Hypokalemia
3) Elevated Aldosteronism
4) Low renin
Rx: Dexamethasone
Glucocorticoid -remedial aldosteronism (GRA)
What is Liddle Syndrome?
What are the symptoms:
What are the treatment options:
An autosomal dominant mutation that mimics hyperaldosteronism that decreases degradation of sodium channels in the CCT (hypernatremia)
It classically presents in children as:
1) HTN
2) Hypokalemia
3) Metabolic acidosis
4) Low Renin & Low Aldosterone
Rx: Give K+ sparring diuretics (amiloride or triamterene) to block Na+ channels in the CCT
An autosomal dominant mutation that mimics hyperaldosteronism that decreases degradation of sodium channels in the CCT (hypernatremia)
It classically presents in children as:
1) HTN
2) Hypokalemia
3) Metabolic acidosis
4) Low Renin & Low Aldosterone
Rx: Give K+ sparring diuretics (amiloride or triamterene) to block Na+ channels in the CCT
Liddle Syndrome
What is SAME (Syndrome of Apparent Mineralcorticoid Excess)?
What are the symptoms:
What is the diagnostic test:
An autosomal recessive mutation that mimics hyperaldosteronism. It results in 11B-hydroxysteroid dehydrogenase 2 (11B-HSD2) deficiency which allows cortisol to activate renal aldosterone receptors.
It classically presents in children as:
1) HTN
2) Hypokalemia
3) Metabolic alkalosis
4) Low Renin & Low Aldosteronism
Tests: Low urine free cortisone
An autosomal recessive mutation that mimics hyperaldosteronism. It results in 11B-hydroxysteroid dehydrogenase 2 (11B-HSD2) deficiency which allows cortisol to activate renal aldosterone receptors.
It classically presents in children as:
1) HTN
2) Hypokalemia
3) Metabolic alkalosis
4) Low Renin & Low Aldosteronism
Tests: Low urine free cortisone
SAME (Syndrome of Apparent Mineralcorticoid Excess)
What is Cushing syndrome?
What are the symptoms:
What are the lab findings:
What are the diagnostic tests:
A condition with excessive cortisol production (fasciculata) that can be caused by adrenal lesions or adrenal tumors.
It presents as:
1) Muscle weakness/thin extremities
2) Moon face & Buffalo hump
3) Truncal obesity
4) Purple abdominal striae
5) HTN with hypokalemia & metabolic alkalosis
6) Osteoporosis
7) Immunosuppression
Labs show:
1) Elevated 24hr urine cortisol & late night salivary cortisol level
2) Low dose dexamethasone suppression test
ACTH test:
ACTH-independent means it is due to a lesion
ACTH-dependent means it is due to a tumor
A condition with excessive cortisol production (fasciculata) that can be caused by adrenal lesions or adrenal tumors.
It presents as:
1) Muscle weakness/thin extremities
2) Moon face & Buffalo hump
3) Truncal obesity
4) Purple abdominal striae
5) HTN with hypokalemia & metabolic alkalosis
6) Osteoporosis
7) Immunosuppression
Labs show:
1) Elevated 24hr urine cortisol & late night salivary cortisol level
2) Low dose dexamethasone suppression test
ACTH test:
ACTH-independent means it is due to a lesion
ACTH-dependent means it is due to a tumor
Cushing syndrome
ACTH-independent means it is due to a _____
ACTH-dependent means it is due to a _____
ACTH independent = adrenal lesion
ACTH dependent = ACTH secreting pituitary tumor
What are the lab findings you would expect to see in a patient with Cushing’s?
Labs show:
1) Elevated 24hr urine cortisol & late night salivary cortisol level
2) Low dose dexamethasone suppression test
Labs show:
1) Elevated 24hr urine cortisol & late night salivary cortisol level
2) Low dose dexamethasone suppression test
Cushing’s
Distinguishing the cause of Cushing’s
Usually due to an Iatrogenic cause:
Low ACTH
No imaging
No response to dexamethasone suppression test
Exogenous glucocorticoids
Distinguishing the cause of Cushing’s
Elevated ACTH & Androgens
Suppression with high dose of dexamethasone
Adenoma on imaging
Pituitary adenoma
Distinguishing the cause of Cushing’s
Very high ACTH
Excessive Androgens
Hyperpigmentation
No suppression to a high dose of dexamethasone
Surgical resection is needed
Ectopic ACTH secretion i.e Small cell carcinoma or carcinoma
Distinguishing the cause of Cushing’s
Low ACTH
No response to high dose dexamethasone
Imaging shows a mass on adrenal gland
Surgical resection is needed
Primary adrenal adenoma, hyperplasia, or carcinoma
What is Congenital adrenal hyperplasia?
An autosomal recessive condition that causes enzymatic defects in cortisol production. These include:
21-Hydroxylase deficiency
11-Hydroxylase deficiency
17-Hydroxylase deficiency
An autosomal recessive condition that causes enzymatic defects in cortisol production. These include:
21-Hydroxylase deficiency
11-Hydroxylase deficiency
17-Hydroxylase deficiency
Describes which condition?
Congenital adrenal hyperplasia
What is 21-Hydroxylase deficiency?
What are the lab findings:
What are the symptoms:
What is the non-classical presentation:
The most common deficiency caused by congenital adrenal hyperplasia (auto rec).
Labs show:
Low Aldosterone & Low Cortisol
Elevated Androgens
It classically presents in neonates as:
1) Hyponatremia
2) Hyperkalemia
3) Life-threatening hypotension (salt-wasting type)
4) Clitoral enlargement in females (genital ambiguity)
Non-classically it presents later in life with excess androgens:
1) Precocious puberty in males
2) Hirsutism with menstrual irregularities in females
The most common deficiency caused by congenital adrenal hyperplasia (auto rec).
Labs show:
Low Aldosterone & Low Cortisol
Elevated Androgens
It classically presents in neonates as:
1) Hyponatremia
2) Hyperkalemia
3) Life-threatening hypotension (salt-wasting type)
4) Clitoral enlargement in females (genital ambiguity)
Non-classically it presents later in life with excess androgens:
1) Precocious puberty in males
2) Hirsutism with menstrual irregularities in females
21-Hydroxylase deficiency
What is the non-classical presentation of 21-Hydroxylase deficiency?
Non-classically it presents later in life with excess androgens:
1) Precocious puberty in males
2) Hirsutism with menstrual irregularities in females
What is the classical presentation of 11-Hydroxylase deficiency?
A result of congenital adrenal hyperplasia that results in excessive androgens & weak mineralocorticoid (DOC aka Deoxycorticosterone).
A result of congenital adrenal hyperplasia that results in excessive androgens & weak mineralocorticoid (DOC aka Deoxycorticosterone).
It classically presents as:
1) HTN (Na+ retention)
2) Mild hypokalemia
3) Low renin & Low Aldosterone
4) Clitoral enlargement
11-Hydroxylase deficiency
How does 11-Hydroxylase deficiency classically present as?
It classically presents as:
1) HTN (Na+ retention)
2) Mild hypokalemia
3) Low renin & Low Aldosterone
4) Clitoral enlargement
What is 17-Hydroxylase deficiency?
It leads to reduced cortisol levels & androgens.
It presents with:
1) HTN
2) Mild hypokalemia
3) Low renin & Low aldosterone
4) Primary amenorrhea & no pubic hair
5) Ambiguous genitalia with undescended testes
It leads to reduced cortisol levels & androgens.
It presents with:
1) HTN
2) Mild hypokalemia
3) Low renin & Low aldosterone
4) Primary amenorrhea & no pubic hair
5) Ambiguous genitalia with undescended testes
17-Hydroxylase deficiency
It presents with:
1) HTN
2) Mild hypokalemia
3) Low renin & Low aldosterone
4) Primary amenorrhea & no pubic hair
5) Ambiguous genitalia with undescended testes
17-Hydroxylase deficiency
Newborns are screened for Congenital Adrenal Hyperplasia by evaluating the levels of 17-Hydroxyprogesterone
If elevated it indicates ________
Increased 21 & 11 Hydroxylase deficiency
Newborns are screened for Congenital Adrenal Hyperplasia by evaluating the levels of 17-Hydroxyprogesterone
If reduced it indicates ________
17 hydroxylase deficiency
21 Hydroxylase deficiency is treated with what?
Glucocorticoids
17 Hydroxylase deficiency is treated with what?
Sex steroids
What is acute adrenal insufficiency?
An acute insufficiency of adrenal hormones that presents as weakness & shock
It has multiple causes:
1) Abrupt withdrawal from glucocorticoids
2) Receiving treatment for Cushing’s
3) Waterhouse-Friderichsen syndrome
An acute insufficiency of adrenal hormones that presents as weakness & shock
It has multiple causes:
1) Abrupt withdrawal from glucocorticoids
2) Receiving treatment for Cushing’s
3) Waterhouse-Friderichsen syndrome
Rx: gluco & mineralo corticoids
acute adrenal insufficiency
What is Waterhouse Friderichsen syndrome & what adrenal-specific condition can it lead to?
It is hemorrhagic necrosis of the adrenal glands classically due to sepsis or DIC in young children with an N. meningitidis infection. It can cause acute adrenal insufficiency
It is hemorrhagic necrosis of the adrenal glands classically due to sepsis or DIC in young children with an N. meningitidis infection. It can cause acute adrenal insufficiency
Waterhouse Friderichsen syndrome
What is Addisons disease?
aka chronic adrenal insufficiency, it usually arises in conditions that lead to progressive adrenal damage (autoimmune, TB, Metastatic carcinoma (lung), secondary (Pituitary) or tertiary (hypothalamus)
aka chronic adrenal insufficiency, it usually arises in conditions that lead to progressive adrenal damage (autoimmune, TB, Metastatic carcinoma (lung), secondary (Pituitary) or tertiary (hypothalamus)
It presents as vague/progressive symptoms:
1) Hypotension
2) Fatigue/weakness
3) N/V/Weight-loss
Labs show:
- Hyperpigmentation (high ACTH) & Hypokalemia (low Aldosterone) indicates the cause as primary adrenal insufficiency
- No ACTH response to Metyrapone stimulation suggests secondary or tertiary causes
- ACTH responses to CRH stimulation indicated tertiary cause (hypothalamus-related)
Addisons disease
What does Hyperpigmentation (high ACTH) & Hypokalemia (low Aldosterone) in Addison’s disease indicate?
the cause as primary adrenal insufficiency
What does No ACTH response to Metyrapone stimulation suggest?
It can be due to secondary or tertiary causes
What does ACTH responses to CRH stimulation indicate?
A tertiary cause (hypothalamus-related)
What is a pheochromocytoma?
A tumor of chromaffin cells that episodically release catecholamines.
It is associated with genotypes MEN2A/2B, Von Hipple Lindau & Neurofibrosis type 1
How is malignancy defined in pheochromocytomas?
By metastatic spread
A tumor of chromaffin cells that episodically release catecholamines.
It is associated with genotypes MEN2A/2B, Von Hipple Lindau & Neurofibrosis type 1
It presents as:
1) HTN
2) Headaches
3) Palpitations
4) Tachycardia
5) Sweating
Labs show:
Elevated catecholamines in the serum/urine
Rx: Adrenalectomy
pheochromocytoma
What is the rule of 10 regarding a pheochromocytoma?
10% are bilateral, familial, malignant, or outside the adrenal medulla
It presents as:
1) HTN
2) Headaches
3) Palpitations
4) Tachycardia
5) Sweating
pheochromocytoma
